, Volume 40, Issue 3, pp 412–448 | Cite as


A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Use in Asthma and Allergic Disorders
  • Susan M. Grant
  • Karen L. Goa
  • Andrew Fitton
  • Eugene M. Sorkin
Drug Evaluation




Ketotifen is an orally active prophylactic agent for the management of bronchial asthma and allergic disorders. Accumulated evidence indicates that after 6 to 12 weeks of administration, ketotifen significantly reduces respiratory symptoms and the need for concomitant antiasthmatic drugs in about 70% and 50%, respectively, of patients with mild to moderate bronchial asthma. However, absolute improvement in lung function is generally slight. Ketotifen also has pronounced antihistaminic and antianaphylactic properties which result in moderate to marked symptom improvement in the majority of patients with atopic dermatitis, seasonal or perennial rhinitis, allergic conjunctivitis, chronic or acute urticaria or food allergy.

Comparative trials with established agents — notably sodium cromoglycate (cromolyn sodium) in asthma and histamine H1- antagonists in allergic disorders — indicate that ketotifen has comparable clinical utility. Unlike inhaled sodium cromoglycate, ketotifen ameliorates the symptoms of asthma, rhinitis and dermatitis when present together in atopic patients.

Patient acceptance of ketotifen is good, although sedation can be troublesome in older children and adults for the initial 2 weeks of treatment. Weight gain is another notable effect in a small percentage of patients.

Thus, ketotifen appears to be a useful agent for the management of allergic disorders and bronchial asthma, particularly in patients for whom oral therapy is preferred. Although a lengthy run-in period is needed in the treatment of asthma, in those patients who respond, continued reduction in the frequency and severity of symptoms and in the use of additional antiasthmatic drugs can be anticipated.

Pharmacodynamic Properties

Ketotifen inhibits the bronchial response to inhaled histamine, allergen or aspirin, and the ocular, nasal and dermal responses to applied allergen in sensitised subjects. Ketotifen and clemastine have similar protective effects against histamine challenge, and ketotifen is generally as effective as sodium cromoglycate against both early and late reactions precipitated by inhalation of allergen extract in patients with extrinsic asthma. In contrast, ketotifen does not protect against methacholine- or exercise-induced bron-choconstriction.

Chronic inflammatory changes associated with the recruitment and activation of eosinophils within the tracheobronchial tree appear to underlie the changes in airway patency and reactivity in chronic asthma. Prior treatment with ketotifen attenuated airway eosinophilia and the ensuing hyperreactivity in animals, but similar data in humans are currently lacking. Inhibition of the release and/or activity of proinflammatory mediators, which has been demonstrated in vitro or in animals for histamine, platelet-activating factor (PAF), arachidonic acid metabolites, neutrophil chemotactic factor, and the cytotoxic oxygen intermediate O2 , may contribute to the prophylactic effect of ketotifen. Calcium may be integral to the generation and/or release of some of these compounds and a number of studies suggest that ketotifen interferes with calcium flux. It does not appear to affect smooth muscle contraction. Additional possible modes of action of ketotifen include its ability to reverse β2-agonist-induced reductions in β-adrenoceptor density and to alter the affinity of these receptors and increase intracellular concentrations of cyclic adenosine monophosphate (cAMP).

Exposure to ketotifen in vitro or in vivo had no clinically important effect on the number or function of lymphocytes in asthmatic children but the drug has been reported to decrease serum IgE levels and eosinophil counts in patients with bronchial asthma.

Pharmacokinetic Properties

Ketotifen is well absorbed after oral administration, achieving peak plasma concentrations within 2 to 4 hours of administration in conventional dosage forms. However, information regarding absorption from the once-daily slow-release tablet is lacking. Due to a ‘first pass’ effect, bioavailability of the drug is only about 50%. Peak plasma concentrations after multiple oral doses of 1mg twice daily were 1.92 mg/L in adults and 3.25 mg/L in children, with corresponding areas under the concentration-time curve of 16.98 mg/L· h and 20.72 mg/L· h. The drug is reported to be 75% protein bound.

Ketotifen is extensively metabolised to the inactive ketotifen-N-glucuronide and the pharmacologically active nor-ketotifen, and recovery of these metabolites in urine accounts for 50% and 10% of the administered dose, respectively. Only 1% is retrievable as the parent compound. Clearance of the drug from plasma is biphasic, with a half-life of distribution of 3 hours and a half-life of elimination of 22 hours in adults. Children exhibit a similar pattern of elimination. No data are available with regard to the effect of advanced age or disease on the pharmacokinetic profile of ketotifen.

Therapeutic Use

Although there is a large body of data available on the clinical use of ketotifen, poor study design, critical to the evaluation of a prophylactic drug, limits the usefulness of some studies. In well-designed trials the drug improved respiratory symptoms in about 70% of adults with asthma, based on patient diaries and physician assessment, and permitted a reduction in concomitant antiasthmatic drug requirements in about 50% of patients. The effects were apparent after 6 to 12 weeks and responding patients continued to improve with long term treatment. When initiated 6 to 8 weeks prior to peak pollen season, ketotifen attenuated the symptoms associated with seasonal asthma. Lung function, most frequently measured as peak expiratory flow, did not markedly improve in most studies but did remain stable as bronchodilators were withdrawn. Well-designed comparative trials are divided on whether ketotifen or sodium cromoglycate is statistically superior in patients with asthma. In general, the improvements in respiratory symptoms and bronchodilatbr requirements are clinically equivalent for these 2 agents and the preference of the individual and subsequent response will be the best guide when deciding on long term treatment. Limited comparative experience with ketotifen, azelastine and picumast suggests these 3 oral agents are similarly effective in the management of asthma.

Although some investigators reported ketotifen to be no more effective than placebo when used to treat children with asthma, when studies permitting concomitant sodium cromoglycate were excluded from analysis significant reductions in asthma symptoms and bronchodilator or theophylline requirements were demonstrated with the active drug. Well-designed comparisons with sodium cromoglycate are sparse but suggest that, in children as in adults, ketotifen reduces symptoms and drug requirements to a similar degree.

Several studies have addressed the possibility of corticosteroid withdrawal in ketotifen-treated patients with more severe steroid-dependent asthma. The results suggest that reduction in steroid dosage is possible in selected patients but there is currently little evidence that ketotifen can replace oral or inhaled corticosteroids in dependent patients. Prevention of asthma with ketotifen would be ideal; studies in at-risk infants hint at a protective effect for ketotifen and its use in this setting merits further study.

Ketotifen is effective in relieving the nasal and ocular symptoms of perennial and seasonal rhinitis in adults and children, the improvement being most pronounced in children with seasonal symptoms. The drug was at least as effective as clemastine, chlorpheniramine (chlorphenamine), terfenadine, loratadine or insufflated sodium cromoglycate in comparative trials but was less effective than astemizole in 1 study.

Good and sometimes dramatic improvement was noted in patients with chronic or cold- or exercise-induced urticaria treated with ketotifen for 1 to 4 weeks. The response in patients with urticaria pigmentosa or systemic mastocytosis was less impressive although good responses have been reported in individuals with this disorder and in small groups of patients with neurofibromatosis. Despite the variable nature of atopic dermatitis, a good response has been clearly demonstrated for ketotifen, including a decrease in skin lesions and pruritus over the course of 4 to 9 weeks’ treatment.

Food intolerance or allergy often appear as symptoms in several body systems (e.g. skin, gastrointestinal tract, lungs), and while elimination of the offending food(s) is effective it may impose unacceptable lifestyle and nutritional hardships. Prophylactic use of ketotifen appears to prevent bronchospasm, urticaria, skin lesions and gastrointestinal upset invoked by food allergens and may allow the reintroduction of poorly tolerated foods.

Adverse Effects

Ketotifen is generally well tolerated, especially in young children. The most frequent adverse effect is sedation, which occurs in about 10 to 20% of patients but declines after I to 2 weeks of continued use. Other reactions including dizziness, dry mouth, nausea and headache have been reported in 1 to 2% of patients after initiating therapy but do not appear to persist in patients continuing with long term treatment (up to 12 months). Weight gain may also occur in a small percentage of patients.

Dosage and Administration

For adult patients with bronchial asthma or allergic disease, the recommended dosage of ketotifen is 2 mg/day divided into 2 doseS or given as a single slow-release tablet. Patients should be cautioned against operating machinery or performing tasks requiring psychomotor skills until the sedative effects of the drug, if any, are known. If sedation is considered a problem, therapy should be initiated at half the daily dose or the drug should be given at bedtime.

Children aged 6 months to 3 years should be given ketotifen (tablet or syrup) in a dosage of 0.5mg twice daily, but older children should receive the full adult dose.


Asthma Atopic Dermatitis Cromoglycate Peak Expiratory Flow Sodium Cromoglycate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ackerman SJ. The new Gestalt: asthma as a chronic inflammatory disease. Journal of Asthma 26: 331–333, 1989PubMedCrossRefGoogle Scholar
  2. Adachi M, Kamiya I, Sato H, Nishikata H, Hoshino H, et al. Ketotifen inhibits airway hyperresponsiveness (AHR) induced by platelet activating factor (PAF). Abstract 894. New England and Regional Allergy Proceedings 9: 472, 1988Google Scholar
  3. Adachi M, Kobayashi H, Aoki N, Iijima M, Kokubu F, et al. A comparison of the inhibitory effects of ketotifen and disodium cromoglycate on bronchial responses to house dust, with special reference to the late asthmatic response. Pharmatherapeutica 4: 36–42, 1984PubMedGoogle Scholar
  4. Ambrosi L, Bariffi F, Carino M, Catena E, Ceccarelli G, et al. Azelastine in the prophylactic treatment of bronchial asthma: an Italian multicentre comparison with ketotifen. Journal of International Medical Research 17: 218–225, 1989PubMedGoogle Scholar
  5. Armour C, Temple DM. The modification by ketotifen of respiratory responses to histamine and antigen in guinea-pigs. Agents and Actions 12: 285–288, 1982PubMedCrossRefGoogle Scholar
  6. Arnoux B, Denjean A, Page CP, Nolibe D, Morley J, et al. Accumulation of platelets and eosinophils in baboon lung after PAF-acether challenge. American Review of Respiratory Disease 137: 855–860, 1988PubMedGoogle Scholar
  7. Arruzazabala ML, Alvarez RG, Pérez JS. Involvement of calcium ions in the mode of action of disodium cromoglycate and ketotifen on smooth muscle. Allergologia et Immunopathologia 11: 15–18, 1983PubMedGoogle Scholar
  8. Asrilant M, Zelazco M. Actividad profilactica del ketotifeno en el asma bronquial extrinseca. Prensa Médica Argentina 69: 548–556, 1982Google Scholar
  9. Bakran Jr I, Cvoriscec B, Durakovic Z. Ketotifen versus disodium cromoglycate (DSCG) in allergic bronchial asthma. Respiration 42 (Suppl. 1): 115–116, 1981Google Scholar
  10. Baronti A, Grieco A, Virgilli G, Lelli IM, Vibelli C. Effects of acutely administered ketotifen on specific bronchial provocation tests. Current Therapeutic Research 33: 936–940, 1983Google Scholar
  11. Baronti A, Vibelli C. Ketotifen in skin-test-positive perennial asthma. Current Therapeutic Research 33: 401–407, 1983Google Scholar
  12. Benincori N, Ferrara M, Cantani A, Nini G, Trogolo E, et al. Valutazione dell’efficacia del chetotifene nella prevenzione delle esacerbazioni della dermatite atopica da intolleranza alimentare del bambino. Folia Allergologica et Immunologica Clinica 35: 399–408, 1988Google Scholar
  13. Bernstein IL, Hargreave FE, Nicklas RA, Reed CE. Report of the American Academy of Allergy and Immunology Task Force on guidelines for clinical investigation of nonbronchodilator antiasthmatic drugs. Journal of Allergy and Clinical Immunology 78: 489–541, 1986CrossRefGoogle Scholar
  14. Bierman W, Pierson W, Shapiro G, Furukawa C, Sharpe M. Ketotifen reduces bronchial hyperreactivity in children. Abstract 240. Journal of Allergy and Clinical Immunology 49: 184, 1987Google Scholar
  15. Boner AL, Richelli C, Antolini I, Vibelli C, Andri L. The efficacy of ketotifen in a controlled double-blind food challenge study in patients with food allergy. Annals of Allergy 57: 61–64, 1986PubMedGoogle Scholar
  16. Braquet P, Touqui L, Shen TY, Vargaftig BB. Perspectives in platelet-activating factor research. Pharmacological Reviews 39: 97–145, 1987PubMedGoogle Scholar
  17. Broberger U, Graff-Lonnevig V, Lilja G, Rylander E. Ketotifen in pollen-induced asthma: a double blind placebo-controlled study. Clinical Allergy 16: 119–127, 1986PubMedCrossRefGoogle Scholar
  18. Brodde O-E, Brinkmann M, Schemuth R, O’Hara N, Daul A. Terbutaline-induced desensitization of human lymphocyte β2-adrenoceptors. Journal of Clinical Investigation 76: 1096–1101, 1985PubMedCrossRefGoogle Scholar
  19. Brodde O-E, Howe U, Egerszegi S, Konietzko N, Michel MC. Effect of prednisolone and ketotifen on β2-adrenoceptors in asthmatic patients receiving β2-bronchodilators. European Journal of Clinical Pharmacology 34: 145–150, 1988PubMedCrossRefGoogle Scholar
  20. Businco L, Bellioni P, Benincori N, Bruno G, DiCicco C, et al. Oral ketotifen versus disodium cromoglycate nasal spray for the prophylactic treatment of pollen-induced allergic manifestations. Current Therapeutic Research 35: 239–246, 1984Google Scholar
  21. Cardoso RR. Prophylaxis against bronchial asthma evaluation of a new therapeutic agent, ketotifen, with a bronchial challenge test. Folha Médica 81: 565–567, 1980Google Scholar
  22. Carnimeo N, Resta O, Foschino-Barbaro MP, Maiorano V. Protective effect of ketotifen against bronchoconstriction induced by ASA inhalation. Current Therapeutic Research 30: 807–811, 1981Google Scholar
  23. Carpentiere G, Marino S, Castello F, Baldanza C, Bonanno CT. Effect of ketotifen on the time-course of methacholine-induced bronchoconstriction. Current Therapeutic Research 45: 1071–1076, 1989Google Scholar
  24. Carrasco E, Galleguillos F, Bernath Z. The orally administered anti-allergic agent, ketotifen; efficacy in atopic and non-atopic bronchial asthma. Allergologia et Immunopathologia 9: 335–342, 1981PubMedGoogle Scholar
  25. Castello D, De Candussio G, Franchi D, et al. Studio a medio termine dell’attività e delle tollerabilità del chetotifene in pediatria e confronto con il disodiocromoglicato. Giornale Italiano delle Malattie di Torace 39: 285–289, 1985Google Scholar
  26. Castillo JG, Oehling A, Gamboa PM, Sanz ML, Garcia BE. Effect of ketotifen on adenyl cyclase activity in asthmatic patients. Allergologia et Immunopathologia 16: 151–156, 1988PubMedGoogle Scholar
  27. Castillo JG, Sanz ML, Oehling A. Action of ketotifen on histamine release and intracellular cAMP levels in basophil cultures from pollinic subjects. Allergologia et Immunopathologia 14: 107–113, 1986PubMedGoogle Scholar
  28. Chung KF, Barnes PJ. PAF Antagonists: their potential therapeutic role in asthma. Drugs 35: 93–103, 1988PubMedCrossRefGoogle Scholar
  29. Chung KF, Minette P, McCusker M, Barnes PJ. Ketotifen inhibits the cutaneous but not the airway responses to platelet-activating factor in man. Journal of Allergy and Clinical Immunology 81: 1192–1198, 1988PubMedCrossRefGoogle Scholar
  30. Chyrek-Borowska S, Hofman J, Siergiejko Z. Effect of ketotifen on the blood histamine level in atopic patients and on histamine release from mouse mast cells exposed to specific antigen and C. 48/80. In Proceedings, annual meeting of the European Academy of Allergology and Clinical Immunology, Vol. 2, pp. 811–815, Clermont-Ferrand, Sep 1981Google Scholar
  31. Clauzel AM, Calvayrac P, Michel FB, Mourad C. Essai double insu double placebo de ketotifene et de cromoglycate de sodium dans le traitement de l’asthme. Provence Médicale 48: 78–82, 1980Google Scholar
  32. Clough JB, Holgate ST. The natural history of bronchial hyper-responsiveness. Clinical Reviews in Allergy 7: 257–278, 1989PubMedGoogle Scholar
  33. Contreras G, Lisboa C, Vasquez E, Ferretti R, Cruz E. Efecto de la administracion prolongada de ketotifeno sobre la reactividad bronquial y la medicacion en asmaticos. Revista Médica de Chile 114: 623–631, 1986PubMedGoogle Scholar
  34. Corrias A, Rossi G, Nardi MG. II chetotifene nel trattamento dell’eczema atopico infantile. Pediatria Medica e Chirurgica 7: 881–885, 1985PubMedGoogle Scholar
  35. Craps L, Greenwood C, Radielovic P. Clinical investigation of agents with prophylactic anti-allergic effects in bronchial asthma. Clinical Allergy 8: 373–382, 1978PubMedCrossRefGoogle Scholar
  36. Craps LP, Ney UM. Ketotifen: current views on its mechanism of action and their therapeutic implications. Respiration 45: 411–421,1984PubMedCrossRefGoogle Scholar
  37. Czarnetzki BM. A double-blind crossover study of the effect of ketotifen in urticaria pigmentosa. Dermatologica 166: 44–47, 1983PubMedCrossRefGoogle Scholar
  38. Czerniawska-Mysik G, Woloszynski J, Adamek-Guzik T, Koterba A, Prochowska K, et al. Proceedings, annual meeting of the European Academy of Allergology and Clinical Immunology. Vol. 2, pp. 828–830, Clermont-Ferrand, Sep 1981Google Scholar
  39. Dal Negro RW, Turco P, Zoccatelli O, Trevisan F, Pomari C. Prevention of bronchial hyperreactivity in atopic asthmatics during the period of maximal allergenic risk: a six-month study. International Journal of Clinical Pharmacology, Therapy and Toxicology 24: 100–103, 1986Google Scholar
  40. Dawson KP, Fergusson DM, Horwood LJ, Mogridge N. Ketotifen in asthma. Australian Paediatric Journal 25: 89–92, 1989PubMedGoogle Scholar
  41. Delaney JC. The effect of ketotifen on aspirin-induced asthmatic reactions. Clinical Allergy 13: 247–251, 1983PubMedCrossRefGoogle Scholar
  42. Devillier P, Arnoux B, Lalau Keraly C, Landes A, Marsac J, et al. Inhibition of human and rabbit platelet activation by ketotifen. Fundamental Clinical Pharmacology 4: 1–9, 1990PubMedCrossRefGoogle Scholar
  43. Dorow P, Schiess W. The influence of ketotifen and aminophylline on the central and peripheral airways. Arzneimittel-Forschung 33: 265–268, 1983PubMedGoogle Scholar
  44. Dorow P, Schiess W. Influence of ketotifen on the airway responsiveness in asthmatics. Journal of Asthma 21: 81–88, 1984PubMedCrossRefGoogle Scholar
  45. Dorward AJ, Kerr JW, Patel KR. The effect of long term ketotifen on exercise induced asthma and histamine release. Australian and New Zealand Journal of Medicine 14 (Suppl. 2): 531, 1984Google Scholar
  46. Dorward AJ, Patel KR. A comparison of ketotifen with clemastine, ipratropium bromide and sodium cromoglycate in exercise-induced asthma. Clinical Allergy 12: 355–361, 1982PubMedCrossRefGoogle Scholar
  47. Dorward AJ, Patel KR. Inhaled ketotifen in exercise-induced asthma — a negative report. European Journal of Respiratory Disease 67: 378–380, 1985Google Scholar
  48. Dutau G, Sablayrolles B, Pienkowski C, Rochiccioli P. Traitement du syndrome asthmatique du nourrisson par le kétotiféne. Annales de Pediatric 33: 363–367, 1986Google Scholar
  49. El Hefny A, El Beshlawy A, Nour S, Said M. Ketotifen in the treatment of infants and young children with wheezy bronchitis and bronchial asthma. Journal of International Medical Research 14: 267–273, 1986PubMedGoogle Scholar
  50. Ellul-Micallef R. Effect of oral sodium cromoglycate and ketotifen in fish-induced bronchial asthma. Thorax 38: 527–530, 1983PubMedCrossRefGoogle Scholar
  51. Esau S, del Carpio J, Martin JG. A comparison of the effects of ketotifen and clemastine on cutaneous and airway reactivity to histamine and allergen in atopic asthmatic subjects. Journal of Allergy and Clinical Immunology 74: 270–274, 1984PubMedCrossRefGoogle Scholar
  52. Fernandez M, Wong E, Oehling A. Retrospective study of ketotifen protective action in different allergopathies. Allergologia et Immunopathologia 15: 369–373, 1987PubMedGoogle Scholar
  53. Fiocchi A, Riva E, Borella E, Arensi D, Giovannini M. Ketotifen treatment of atopic dermatitis in childhood. Current Therapeutic Research 37: 1113–1123, 1985Google Scholar
  54. Furlan J, Suskovic S, Gashi A. Preventive effect of ketotifen on bronchoconstriction induced by food allergens. Respiration 46 (Suppl.): 16, 1984Google Scholar
  55. Furlan J, Suskovic S, Rus A. The effect of food on the bronchial response in adult asthmatic patients, and the protective role of ketotifen. Allergologia et Immunopathologia 15: 73–81, 1987PubMedGoogle Scholar
  56. Garty M, Scolnik D, Danziger Y, Volovitz B, Ilfeld DN, et al. Non-interaction of ketotifen and theophylline in children with asthma — an acute study. European Journal of Clinical Pharmacology 32: 187–189, 1987PubMedCrossRefGoogle Scholar
  57. Goihman-Yahr M, Rothemberg A, Essenfeld-Yahr E. Erythema multiforme and ketotifen. Journal of the American Academy of Dermatology 8: 429–430, 1983PubMedCrossRefGoogle Scholar
  58. Gonzalez R, Girardi G. A clinical trial of ketotifen in the management of asthma in infants. Immunology and Allergy Practice 10: 222–226, 1988CrossRefGoogle Scholar
  59. Graff-Lonnevig V, Hedlin G. The effect of ketotifen on bronchial hyperreactivity in childhood asthma. Journal of Allergy and Clinical Immunology 76: 59–63, 1985PubMedCrossRefGoogle Scholar
  60. Graff-Lonnevig V, Kusoffsky E. Comparison of the clinical effect of ketotifen and DSCG in pollen-induced childhood asthma. Allergy 35: 341–348, 1980PubMedCrossRefGoogle Scholar
  61. Graves L, Stechschulte DJ, Morris DC, Lukert BP. Inhibition of mediator release in systemic mastocytosis is associated with reversal of bone changes. Journal of Bone and Mineral Research, in press, 1990Google Scholar
  62. Greenwood C. The pharmacology of ketotifen. Chest 82 (Suppl.): 45S–48S, 1982PubMedGoogle Scholar
  63. Guibout P, Choffel C, Constans P, Fabre C, Robillard M. Efficacy of ketotifen in adult asthmatic patients: a 6-month double-blind versus placebo study. Respiration 46 (Suppl.): 20, 1984Google Scholar
  64. Gushchin IS, Zebrev AI. Ketotifen-induced histamine release, inhibition of histamine secretion and modulation of immune response. Agents and Actions 18: 92–95, 1986PubMedCrossRefGoogle Scholar
  65. Haahtela T. Comparisons among HC 20-511 (ketotifen), clemastine, DSCG and beclomethasone dipropionate in nasal challenge. Annals of Allergy 41: 345–347, 1978PubMedGoogle Scholar
  66. Hargreave FE, Fink JN, Cockcroft DW, Fish JE, Holgate ST, et al. Workshop 4: the role of bronchoprovocation. Journal of Allergy and Clinical Immunology 78: 517–524, 1986CrossRefGoogle Scholar
  67. Haustein U-F. Ketotifen hemmt Juckreiz und Tumor-progression bei Neurofibromatose. Dermatologische Monatsschrift 175: 581–584, 1989Google Scholar
  68. Herjavecz I, Böszörmeny-Nagy G. Medikamentöse Prophylaxe bei allergischem Asthma bronchiale. Zeitschrift fur Allergologie Medizin 58: 1425–1428, 1982Google Scholar
  69. Hiratani M, Ito S, Muto K, Ueda S. Efficacy of ketotifen in subjects with food allergy. Journal of Allergy and Clinical Immunology 79: 185, 1987Google Scholar
  70. Hruskovic I. Evaluation of prohylactic treatment of asthma in children: a double-blind controlled trial. Allergologia et Immunopathologia 88: 476, 1980Google Scholar
  71. Hsieh K-H. The effect of ketotifen on the in vitro immune function of asthmatic children. Journal of Allergy and Immunology 1: 85–88, 1983Google Scholar
  72. Hsu K, Wang D, Shen C-Y, Hsu Y-S, Shieh S-D. Protective effect of ketotifen on chemiluminescence of neutrophils. Journal of the Formosan Medical Association 87: 939–943, 1988PubMedGoogle Scholar
  73. Hui KK, Yu JL. Ketotifen increases cyclic adenosine 3′,5′-monophosphate in intact human lymphocyte and potentiates other adenylate cyclase activating agents. Life Sciences 40: 1259–1265, 1987PubMedCrossRefGoogle Scholar
  74. Hui KK, Yu JL. Effects of calcium channel blockers and ketotifen on beta2 adrenergic receptor regulation in intact human lymphocytes. Research Communications in Chemical Pathology and Pharmacology 65: 3–19, 1989PubMedGoogle Scholar
  75. Huston DP, Bressler B, Kaliner M, Sowell LK, Baylor MW. Prevention of mast-cell degranulation by ketotifen in patients with physical urticarias. Annals of Internal Medicine 104: 507–510, 1986PubMedGoogle Scholar
  76. Ikari H, Matsunaga T. Clinical evaluation of five-year continuous prophylaxis of children’s bronchial asthma using ketotifen capsule. Improvements in quality of life, serum IgE concentration and peripheral eosinophils. Pediatric Clinics (Japan) 39: 3275–3281, 1989Google Scholar
  77. Ishibashi Y, Harada S, Niimura M, Ueda H, Imamura S, et al. Clinical evaluation of KG-2413 (emedastine difumarate) on chronic urticaria by multicenter double-blind study: comparative study between 2 mg/day, 4 mg/day and ketotifen fumarate. Rinsho Iyaku 1: 141–159, 1990Google Scholar
  78. Joly F, Bessou G, Benveniste J, Ninio E. Ketotifen inhibits pafacether biosynthesis and β-hexosaminidase release in mouse mast cells stimulated with antigen. European Journal of Pharmacology 144: 133–139, 1987PubMedCrossRefGoogle Scholar
  79. Julien-Larose C, Guerret M, Lavene D, Kiechel JR. Quantification of ketotifen and its metabolites in human plasma by gas chromatography mass spectrometry. Biomedical Mass Spectrometry 10: 136–142, 1983PubMedCrossRefGoogle Scholar
  80. Kakuta Y, Kato T, Sasaki H, Takishima T. Effect of ketotifen on human alveolar macrophages. Journal of Allergy and Clinical Immunology 81: 469–474, 1988PubMedCrossRefGoogle Scholar
  81. Kamide R, Niimura M, Ueda H, Imamura S, Yamamoto S, et al. Clinical evaluation of ketotifen for chronic urticaria: multicenter double-blind comparative study with clemastine. Annals of Allergy 62: 322–325, 1989PubMedGoogle Scholar
  82. Kasuya S, Izumi S. Steroid-sparing effect of ketotifen in steroid-dependent asthmatics: a long period evaluation in 12 patients. Pharmatherapeutica 5: 177–182, 1988PubMedGoogle Scholar
  83. Kato T, Terui T, Tagami H. Effects of HC 20-511 (ketotifen) on chemiluminescence of human neutrophils. Inflammation 9: 45–51, 1985PubMedCrossRefGoogle Scholar
  84. Kay AB. Inflammatory cells in bronchial asthma. Journal of Asthma 26: 335–344, 1989PubMedCrossRefGoogle Scholar
  85. Kelly P, Taylor M. Interim report of a double-blind controlled study of ketotifen in childhood asthma. Research and Clinical Forums 4: 35–43, 1982Google Scholar
  86. Kennedy GR. Metabolism and pharmacokinetics of ketotifen in children. Research and Clinical Forums 4: 17–20, 1982Google Scholar
  87. Kennedy GR, Sherriff JM. Comparison of the orally administered anti-allergy agent, ketotifen with sodium cromoglycate in the prophylaxis of bronchial asthma. Respiration 41: 264–269, 1981PubMedCrossRefGoogle Scholar
  88. Kettelhut BV, Berkebile C, Bradley D, Metcalfe DD. A double-blind, placebo-controlled, crossover trial of ketotifen versus hydroxyzine in the treatment of pédiatrie mastocytosis. Journal of Allergy and Clinical Immunology 83: 866–870, 1989PubMedCrossRefGoogle Scholar
  89. Kings MA, Chapman I, Kristersson A, Sanjar S, Morley J. Human recombinant lymphokines and tytokines induce pulmonary eosinophilia in the guinea-pig that is inhibited by ketotifen and AH 21-132. Submitted for publication Kishimoto T, Sato T, Takahashi K, Kimura I. The effect of ketotifen on the reactivity of eosinophils with incubation of anti-IgG. Abstract, no. 900. New England and Regional Allergy Proceedings 9: 473, 1988Google Scholar
  90. Koh YY, Choi JH, Lee BK. The effect of ketotifen in the prophylaxis of bronchial asthma in children: a double-blind comparison with placebo. Journal of the Korean Society of Allergology 8: 215–228, 1988Google Scholar
  91. Konno A, Yamakoshi T, Katagiri J, Fujita Y, Terada N. The effect of topical use of antiallergic drugs on reactivity of the nasal mucosa to histamine. Jibi to Rinsho 36: 257, 1990Google Scholar
  92. Kuokkanen K. A new antihistamine HC20-511 compared with dimetinden (Fenistil Retard) in the treatment of chronic urticaria and other pruritic dermatoses. Acta Allergologica 30: 73–79, 1975PubMedGoogle Scholar
  93. Lane DJ. A steroid sparing effect of ketotifen in steroid-dependent asthmatics. Clinical Allergy 10: 519–525, 1980PubMedCrossRefGoogle Scholar
  94. Langrick AF, Wallace lyiG. A new approach to the treatment of seasonal allergic rhinitis. British Journal of Clinical Practice 36: 312–314, 1982PubMedGoogle Scholar
  95. Le Bigot JF, Begue JM, Kiechel JR, Guillouzo A. Species differences in metabolism of ketotifen in rat, rabbit and man: demonstration of similar pathways in vivo and in cultured hepatocytes. Life Sciences 40: 883–890, 1987PubMedCrossRefGoogle Scholar
  96. Le Bigot JF, Cresteil T, Kiechel JR, Beaune P. Metabolism of ketotifen by human liver microsomes. Drug Metabolism and Disposition 11: 585–589, 1983PubMedGoogle Scholar
  97. Lech B, Girard J-P. Bronchial asthma induced by mediators produced in vitro by sensitized lymphomonocytes: protective effect of ketotifen. Allergologia et Immunopathologia 15: 191–194, 1987PubMedGoogle Scholar
  98. Leclercq-Foucart J, Fernere A, Vanden Bussche G. A double-blind trial comparing astemizole and ketotifen in the suppression of hay fever symptoms. Current Therapeutic Research 39: 875–883, 1986Google Scholar
  99. León G, Arellano I. Tolerancia y eficacia del ketotifeno en ninos con dermatitis atöpica. Dermatologia (Méx.) 33: 153–160, 1989Google Scholar
  100. Lilja G, Graff-Lonnevig V, Bevegård S. Comparison of the protective effect of ketotifen and disodium cromoglycate on exercise-induced asthma in asthmatic boys. Allergy 38: 31–35, 1983PubMedCrossRefGoogle Scholar
  101. Lisboa C, Moreno R, Cruz E, Barja S, Sanchez I, et al. Acute effect of ketotifen on the dose-response curve of histamine and methacholine in asthma. British Journal of Diseases of the Chest 79: 235–243, 1985PubMedCrossRefGoogle Scholar
  102. Longo G, Strinati R, Poli F. Valutazione in doppio cieco del chetotifene verso placebo nelFasma allergico infantile. Rivista Italiana di Pediatria 12: 568–571, 1986Google Scholar
  103. López JGH. Ketotifeno en la profilaxis del asma infantil. Ensayo clinico controlado. Allergologia et Immunopathologia 13: 1–7, 1985Google Scholar
  104. MacDonald GF, Plumley DL, Kobric RT, Kobric M. Normali zation of pulmonary function in bronchial asthma in response to ketotifen prophylaxis: a three-year study. Immunology and Allergy Practice 8: 46–52, 1986Google Scholar
  105. MacDonald GF, Ackermans F, Plumley DL. A double-blind study to clinically evaluate ketotifen in the treatment of bronchial asthma. In Proceedings of the Symposium on Ketotifen, Recent advances in the treatment of asthma, Exerpta Medica, pp. 47–55, Amsterdam, Geneva, 1982Google Scholar
  106. Maclay WP, Crowder D. Post-marketing surveillance of ketotifen (Zaditen®): an interim report. Research and Clinical Forums 4: 51–64, 1982Google Scholar
  107. Maclay WP, Crowder D. Report on Zaditen postmarketing surveillance. Progress in Respiratory Research 20: 182–190, 1985Google Scholar
  108. Maclay WP, Crowder D, Spiro S, Turner P. Postmarketing surveillance: practical experience with ketotifen. British Medical Journal 288: 911–914, 1984PubMedCrossRefGoogle Scholar
  109. Magnussen H. The inhibitory effect of azelastine and ketotifen on histamine-induced bronchoconstriction in asthmatic patients. Chest 91: 855–858, 1987PubMedCrossRefGoogle Scholar
  110. Mallet AI, Norris P, Rendell NB, Wong E, Greaves MW. The effect of disodium cromoglycate and ketotifen on the excretion of histamine and N-methylimidazole acetic acid in urine of patients with mastocytosis. British Journal of Clinical Pharmacology 27: 88–91, 1989PubMedCrossRefGoogle Scholar
  111. Mansfield LE, Taistra P, Santamauro J, Ting S, Andriano K. Inhibition of dermographia, histamine, and dextromethorphan skin tests by ketotifen: a possible effect on cutaneous vascular response to mediators. Annals of Allergy 63: 201–206, 1989PubMedGoogle Scholar
  112. Martin U, Römer D. The pharmacological properties of a new, orally active antianaphylactic compound: ketotifen, a benzocycloheptathiophene. Arzneimittel-Forschung 28: 770–782, 1978PubMedGoogle Scholar
  113. Matejcek M, Irwin P, Neff G, Abt K, Wehrli W. Determination of the central effects of the asthma prophylactic ketotifen, the bronchodilator theophylline, and both in combination: an application of quantitative electroencephalography to the study of drug interactions. International Journal of Clinical Pharmacology, Therapy and Toxicology 23: 258–266, 1985Google Scholar
  114. Mattson K, Poppius H, Ahonen A, Haahtela T, Hurmes R, et al. Comparison of ketotifen, disodium cromoglycate and placebo in the. treatment of adult patients with mild extrinsic asthma. Clinical Allergy 11: 237–242, 1981PubMedCrossRefGoogle Scholar
  115. McClean SP, Arreaza EE, Lett-Brown MA, Grant JA. Refractory cholinergic urticaria successfully treated with ketotifen. Journal of Allergy and Clinical Immunology 83: 738–741, 1989PubMedCrossRefGoogle Scholar
  116. Medici TC, Radielovic P, Morley J. Ketotifen in the prophylaxis of extrinsic bronchial asthma. Chest 96: 1252–1257, 1989PubMedCrossRefGoogle Scholar
  117. Mikuni I, Nakajima A, Kogure F, Uchida Y, Kitano S, et al. Evaluation of ketotifen ophthalmic solution on efficacy and safety on allergic conjunctivitis and vernal conjunctivitis: result on multiclinic open trial. Rinsho Iyaku 4: 2371–2383, 1988Google Scholar
  118. Mikuni I, Nakajima A, Kogure F, Uchida Y, Kitano S, et al. Clinical effect of ketotifen ophthalmic solution on allergic conjunctivitis and vernal conjunctivitis: multicentre double-blind study in comparisons with disodium cromoglycate ophthalmic solution, Rinsho Hyoka 17: 275–297, 1989Google Scholar
  119. Mikuni I, Sato K, Togawa K, Mizushima N. A quantitative tear fluids determination of therapeutic efficacy for allergic conjunctivitis. Tokai Journal of Experimental and Clinical Medicine 9: 35–41, 1984PubMedGoogle Scholar
  120. Miraglia del Giudice M, Capristo AF, Maiello N, Decimo F, Bevacqua GA. Study of the efficacy of ketotifen treatment in asthmatic children under 3 years of age. Current Therapeutic Research 40: 685–693, 1986Google Scholar
  121. Miyasato M, Tsuda S, Kasada M, Iryo K, Sasai Y. The effect of ketotifen on density distribution of eosinophils in patients with atopic dermatitis. Japanese Journal of Inflammation 8: 260–262, 1988Google Scholar
  122. Molkhou P, Dupont C. Ketotifen treatment of atopic dermatitis and other food allergy diseases. Allergy 44 (Suppl.): 117–123, 1989Google Scholar
  123. Moodley I, Davies RJ. Inhibition and stimulation of mediator release from human leucocytes and chopped human lung by ketotifen. Clinical Science 62: 13, 1982Google Scholar
  124. Moreno MV, Fernandez M, de la Cuesta CG, Oehling A. The protective effect of ketotifen in exercise-induced bronchospasm. Allergologia et Immunopathologia 16: 91–94, 1988PubMedGoogle Scholar
  125. Morgan DJR, Cundell D, Moodley I, Davies RJ. Effect of inhaled antihistamine and antiallergic drugs on plasma mediator levels during the immediate asthmatic reaction induced by allergen provocation. Abstract. Thorax 38: 22, 1983CrossRefGoogle Scholar
  126. Morgan DJR, Moodley I, Cundell DR, Sheinman BD, Smart W, et al. Circulating histamine and neutrophil chemotactic activity during allergen-induced asthma: the effect of inhaled anti-histamines and anti-allergic compounds. Clinical Science 69: 63–69, 1985PubMedGoogle Scholar
  127. Morley J, Sanjar S, Newth C. Viewpoint: untoward effects of beta-adrenoceptor agonists in asthma. European Respiratory Journal 3: 228–233, 1990PubMedGoogle Scholar
  128. Morley J, Smith D. Lung inflammation, its significance for asthma therapy. Agents and Actions 26: 31–39, 1989PubMedCrossRefGoogle Scholar
  129. Nagy L, Orosz M. Effect of Zaditen on serum neutrophil chemotactic activity in exercise-induced asthma. Respiration 47: 21–23, 1985PubMedCrossRefGoogle Scholar
  130. Nakayama Y, Tsukamoto T. Long term trial of oral ketotifen-MR on adults with bronchial asthma. Shingaku to Rinsho 38: 1423–1432, 1989Google Scholar
  131. Naspitz CK, Freire CAR. Evaluation of ketotifen in the prophylactic treatment of bronchial asthma in children. Allergologia et Immunopathologia 16: 27–31, 1988PubMedGoogle Scholar
  132. Neijens HJ, Knol K. Oral prophylactic treatment in wheezy infants. Immunology and Allergy Practice 10: 17–23, 1988Google Scholar
  133. Nogawa T, Shinohara O, Taguchi N, Takeuchi Y, Abe T, et al. Long term treatment with ketotifen in infants with bronchiolitis and recurrent wheezy infants. Shonika-Shinryo 50: 2611–2614, 1987Google Scholar
  134. Németh A, Magyar P, Herceg R, Huszti Z. Potassium-induced histamine release from mast cells and its inhibition by ketotifen. Agents and Actions 20: 149–152, 1987PubMedCrossRefGoogle Scholar
  135. Okuda M. Clinical investigation of ketotifen in perennial allergic rhinitis: a double-blind comparative study of ketotifen and clemastine fumarate. Rhinology 22: 171–182, 1984PubMedGoogle Scholar
  136. Okuda M. Prophylactic effect of ketotifen on pollinosis. In Wüthrich & Jäger (Eds) The prophylaxis of allergic rhinitis, pp. 28–35, Excerpta Medica, Amsterdam, 1986Google Scholar
  137. Osvath P, Endre L. Comparison of long term treatment of asthmatic children with hyposensitization, ACTH, DSCG and ketotifen. Allergologia et Immunopathologia 12: 471–477, 1984PubMedGoogle Scholar
  138. Pachor ML, Lunardi C, Nicolis F, Cortina P, Accordini C, et al. Studio sull’effetto del chetotifene in pazienti affetti da intolleranza alimentare. Folia Allergologica et Immunologica Clinica 33: 461–468, 1986Google Scholar
  139. Palmen FMLHG. Antigen bronchial challenge and efficacy after 4 weeks of treatment with ketotifen and disodium cromoglycate. Respiration 44: 103–108, 1983PubMedCrossRefGoogle Scholar
  140. Pastorello E, Zanussi C. Ketotifen in the long-term treatment of aspirin-intolerant patients. Progress in Respiratory Research 19: 401–405, 1985Google Scholar
  141. Petheram IS, Moxham J, Bierman CW, McAllen M, Spiro SG. Ketotifen in atopic asthma and exercise-induced asthma. Thorax 36: 308–312, 1981PubMedCrossRefGoogle Scholar
  142. Phanuphak P, Locharernkul C. Double-blind, placebo-controlled study of ketotifen in chronic urticaria. Journal of Allergy and Clinical Immunology 77: 187, 1986Google Scholar
  143. Phillips MJ, Meyrick Thomas RH, Moodley I, Davies RJ. A comparison of the in vivo effects of ketotifen, clemastine, chlorpheniramine and sodium cromoglycate on histamine and allergen induced weals in human skin. British Journal of Clinical Pharmacology 15: 277–286, 1983PubMedCrossRefGoogle Scholar
  144. Phillips MJ, Ollier S, Davies RJ. Use of anterior rhinometry in nasal provocation challenges with allergen and evaluation of the effects of ketotifen, clemastine and sodium cromoglycate on these responses. Respiration 39 (Suppl. 1): 26–31, 1980PubMedCrossRefGoogle Scholar
  145. Phillips MJ, Oilier S, Gould C, Davies RJ. Effect of antihistamines and antiallergic drugs on responses to allergen and histamine provocation tests in asthma. Thorax 39: 345–351, 1984PubMedCrossRefGoogle Scholar
  146. Pinol J, Carapeto FJ. Ketotifeno en el tratamiento de la urticaria crónica y edema angioneurôtico. Allergologia et Immunopathologia 12: 19–27, 1984PubMedGoogle Scholar
  147. Podleski WK. Pharmacotherapy of food allergy — a neglected option. International Journal of Immunopharmacology 11: 311–326, 1989PubMedCrossRefGoogle Scholar
  148. Podleski WK, Zelenak TM, Schmidt JL. Long term trial of ketotifen in bronchial asthma. Annals of Allergy 52: 406–410, 1984PubMedGoogle Scholar
  149. Poison JB, Lockey RF, Bukantz SC, Lowitt S, Krzanowski Jr JJ, et al. Effects of ketotifen on the responsiveness of peripheral blood lymphocyte β-adrenergic receptors. International Journal of Immunopharmacology 10: 657–663, 1988CrossRefGoogle Scholar
  150. Postma DS, Koëter GH, de Vries K. Clinical expression of airway hyperreactivity in adults. Clinical Reviews in Allergy 7: 321–343, 1989PubMedGoogle Scholar
  151. Prowse K. Ketotifen in adult asthma. British Medical Journal 280: 646, 1980PubMedCrossRefGoogle Scholar
  152. Purello D’Ambrosio F, Tigano V, Lombardo G, Garroccio G, Marcazzo A. L’impiego del chetotifene (Zaditen) nel trattamento dell’asma allergico in gravidanza. Archivo di Medicina Interna 38: 277–286, 1986Google Scholar
  153. Raaijmakers JAM, Wassink GA, Kreukniet J, Terpstra GK. Adrenoceptors in lung tissue: characterization, modulation and relations with pulmonary function. European Journal of Respiratory Diseases 65: 215–220, 1984Google Scholar
  154. Rackham A, Brown CA, Chandra RK, Ho P, Hoogerwerf PE, et al. A Canadian multicenter study with Zaditen (ketotifen) in the treatment of bronchial asthma in children aged 5 to 17 years. Journal of Allergy and Clinical Immunology 84: 286–296, 1989PubMedCrossRefGoogle Scholar
  155. Radermecker M. Inhibition of allergen-mediated histamine release from human cells by ketotifen and oxatomide. Respiration 41: 45–55, 1981PubMedCrossRefGoogle Scholar
  156. Radermecker M, Gustin M, Saint-Remy P. Inhibition of anaphylactic histamine release from human lung by ketotifen. Allergologia et Immunopathologia F: 384–385, 1980Google Scholar
  157. Rebmann H. Ketotifen in der Kombinationstherapie des kindlichen Asthma bronchiale: Einfluss auf Lungenfunktionsparameter für kleine Atemwege. Allergologie 10: 60–63, 1987Google Scholar
  158. Reid JJ. Double-blind trial of ketotifen in childhood chronic cough and wheeze. Immunology and Allergy Practice li: 143–150, 1989Google Scholar
  159. Resta O, Foschino MP, Carnimeo N, Lorenzo LD, Bavoso P. Comparison between ketotifen and clemastine in allergen-induced asthma. Current Therapeutic Research 30: 803–806, 1981Google Scholar
  160. Resta O, Foschino MP, Picca V, Carnimeo N. Evaluation of the effects of ketotifen and clemastine against nasal provocation challenges with allergen. Current Therapeutic Research 35: 235–238, 1984Google Scholar
  161. Riccardi VM. Mast-cell stabilization to decrease neurofibroma growth. Archives of Dermatology 123: 1011–1016, 1987PubMedCrossRefGoogle Scholar
  162. Rokicka-Milewska R, Berek-Pyzik B. Ketotifen use in infants with atopy with recurrent obturative bronchitis. Materia Medica Polona 18: 101–103, 1986Google Scholar
  163. Saito Y, Baba S, Furuuchi I, Shimizu T. Double blind comparative study of terfenadine vs ketotifen on perennial allergic rhinitis. Oto-rhino-laryngology (Tokyo) 31 (Suppl. 7): 963–964, 1988Google Scholar
  164. Sakuma Y, Mita H. Topical ketotifen suppressed ocular provocation for Japanese cedar pollinosis. Japanese Journal of Clinical Ophthalmology 43: 1251–1254, 1989Google Scholar
  165. Sanjar S, Aoki S, Boubekeur K, Chapman ID, Smith D, et al. Eosinophil accumulation in pulmonary airways of guinea-pigs induced by exposure to an aerosol of platelet-activating factor: effect of anti-asthma drugs. British Journal of Pharmacology 99: 267–272, 1990aPubMedCrossRefGoogle Scholar
  166. Sanjar S, Aoki S, Kristersson A, Smith D, Morley J. Antigen challenge induces pulmonary airway eosinophil accumulation and airway hyperreactivity in sensitized guinea-pigs: the effect of anti-asthma drugs. British Journal of Pharmacology 99: 679–686, 1990bPubMedCrossRefGoogle Scholar
  167. Sanjar S, Smith D, Schaeublin E, Kristersson A, Chapman I, et al. The effect of prophylactic anti-asthma drugs on PAF-induced airway hyperreactivity. Japanese Journal of Pharmacology 51: 151–160, 1989PubMedCrossRefGoogle Scholar
  168. Sano Y, Kabe J, Itou K, Miyamoto T. The effect of ketotifen on human lymphocyte β-adrenergic receptors. Japanese Journal of Thoracic Diseases 24: 116–122, 1986PubMedGoogle Scholar
  169. Sasamoto A, Koya N, Obata T, Okuma M, Kishida M, et al. Double blind study of ketotifen: efficacy of short-term administration. Pediatric Clinics (Japan) 39: 3275–3281, 1986Google Scholar
  170. Schlesinger M, Schwartz Y, Bibi H, Shapira H, Fink A, et al. Cellular immunity and suppressor T cell function in asthmatic children on prolonged ketotifen therapy. Journal of Clinical and Laboratory Immunology 27: 139–141, 1988PubMedGoogle Scholar
  171. Schmidt-Redemann B, Breeneisen P, Schmidt-Redemann W, Gonda S. The determination of pharmacokinetic parameters of ketotifen in steady state in young children. International Journal of Clinical Pharmacology, Therapy and Toxicology 24: 496–498, 1986Google Scholar
  172. Schmutzler W, Delmich K, Eichelberg D, Glück S, Greven T, et al. The human adenoidal mast cell. Susceptibility to different secretagogues and secretion inhibitors. International Archives of Allergy and Applied Immunology 77: 177–178, 1985PubMedCrossRefGoogle Scholar
  173. Schubotz R. Long-term study of the protective effect of ketotifen in asthmatic patients. International Congress Series 523: 40–46, 1979Google Scholar
  174. Schuhl JF, Holgado de Cuesta D. A double-blind trial comparing disodium cromoglycate (DSCG), and ketotifen in extrinsic asthmatic children. Clinical Allergy 11: 401–405, 1981PubMedCrossRefGoogle Scholar
  175. Sears MR. A double-blind comparison of ketotifen and disodium cromoglycate in atopic adult asthmatics. Clinical Allergy 13: 253–262, 1983PubMedCrossRefGoogle Scholar
  176. Senna GE, Andri G, Caviglia A, Andri L. Uso del chetotifene nell’orticaria cronica. Dermatologie Clinics 8: 41–45, 1988Google Scholar
  177. Slapke J, Müller S, Boerner D. A one-year double-blind clinical study of the efficacy and tolerability of picumast dihydrochloride versus ketotifen in patients with bronchial asthma. Arzneimittel-Forschung 39: 1368–1372, 1989PubMedGoogle Scholar
  178. Smith D, Sanjar S, Morley J. The effect of prophylactic anti-asthma drugs on PAF-induced platelet accumulation in the thorax of the guinea pig. Japanese Journal of Pharmacology 51: 161–166, 1989PubMedCrossRefGoogle Scholar
  179. Soto J, Tchernitchin AN, Poloni P, Voigt G, Caro B, et al. Effect of ketotifen on the distribution and degranulation of uterine eosinophils in estrogen-treated rats. Agents and Actions 28: 198–203, 1989PubMedCrossRefGoogle Scholar
  180. St-Pierre JP, Kobric M, Rackham A. Effect of ketotifen treatment on cold-induced urticaria. Annals of Allergy 55: 840–843, 1985PubMedGoogle Scholar
  181. Sugiyama H, Nabe M, Miyagawa H, Agrawal DK, Townley RG. Inhibitory effect of ketotifen of LTC release and eosinophil chemotaxis. Abstract 549. Journal on Clinical Immunology 85 (Suppl.): 281, 1990Google Scholar
  182. Szczeklik A, Czerniawska-Mysik G, Adamek-Guzik T, Woloszynski J, Koterba A. Ketotifen versus sodium cromoglycate in the therapy of allergic (extrinsic) bronchial asthma. Respiration 39 (Suppl. 1): 3–9, 1980aPubMedCrossRefGoogle Scholar
  183. Szczeklik A, Czerniawska-Mysik G, Serwonska M. Inhibition by ketotifen of idiosyncratic reactions to aspirin. Allergy 35: 421–424, 1980bPubMedCrossRefGoogle Scholar
  184. Tamura G, Mue S, Takishima T. Protective effects of ketotifen on allergen-induced bronchoconstriction and skin weal. Clinical Allergy 16: 535–541, 1986PubMedCrossRefGoogle Scholar
  185. Tan WC, Lim TK. Double-blind comparison of the protective effect of sodium cromoglycate and ketotifen on exercise-induced asthma in adults. Allergy 42: 315–317, 1987PubMedCrossRefGoogle Scholar
  186. Tanser AR, Elmes J. A controlled trial of ketotifen in exercise-induced asthma. British Journal of Diseases of the Chest 74: 398–402, 1980PubMedCrossRefGoogle Scholar
  187. Tasaka K, Mio M, Okamoto M. Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs. Annals of Allergy 56r464-469, 1986Google Scholar
  188. Taytard A, Vuillemin L, Guenard H, Rio P, Vergeret J, et al. Kinetic of normal platelet in stable asthmatic patients. American Review of Respiratory Disease 135: A388, 1987bGoogle Scholar
  189. Taytard A, Vuillemin L, Guenard H, Rio P, Vergeret J, et al. Platelets kinetic in stable asthmatic patients: effects of ketotifen. American Review of Respiratory Disease 135: A388, 1987aGoogle Scholar
  190. Tholen St, Dieterich HA. Terfenadin versus Ketotifen bei Kindern mit atopischer Dermatitis. Allergologie 12: 60–63, 1989Google Scholar
  191. Ting S. Ketotifen and systemic mastocytosis. Letter. Journal of Allergy and Clinical Immunology 85: 818, 1990PubMedCrossRefGoogle Scholar
  192. Tinkelman DG, Moss BA, Bukantz SC, Sheffer AL, Dobken JH, et al. A multicenter trial of the prophylactic effect of ketotifen, theophyliine and placebo in atopic asthma. Journal of Allergy and Clinical Immunology 76: 487–497, 1985PubMedCrossRefGoogle Scholar
  193. Tinkelman DG, Webb CS, Vanderpool GE, Carroll MS, Spangler DL, et al. The use of ketotifen in the prophylaxis of seasonal allergic asthma. Annals of Allergy 56: 213–217, 1986PubMedGoogle Scholar
  194. Tjwa MKT, Smeets J, Maesen F. Ketotifen and methacholine-induced bronchospasm. Allergy 41: 551–555, 1986PubMedCrossRefGoogle Scholar
  195. Trigg CJ, Davies RJ. Measurement of bronchial responsiveness. Clinical Reviews in Allergy 7: 279–300, 1989PubMedGoogle Scholar
  196. Tsuda S, Miyazato M, Nakima T. Clinical evaluation of an antiallergic, ketotifen-MR, on allergic skin disorder. Shinyaku to Rinsho 38: 1084–1092, 1989Google Scholar
  197. Uehara M, Sawai T, Aeba K. Clinical effect of ketotifen on atopic dermatitis: with special attention to the influence of patient background factors. Acta Dermatologica (Hifuka Kiyo) 83: 211–214, 1988Google Scholar
  198. Wahn U, Müller J. Mast cells and basophils: models for studying the antianaphylactic potency of drugs. Pediatric Pharmacology 3: 287–292, 1983PubMedGoogle Scholar
  199. Wang SSM, Wang SR, Chiang BN. Suppressive effects of oral ketotifen on skin responses to histamine, codeine, and allergen skin tests. Annals of Allergy 55: 57–61, 1985PubMedGoogle Scholar
  200. Wang SSM, Wang SR, Shieh WS. The inhibitory effects of ketotifen on SRS activity and SRS production from human leukocytes. Journal of Allergy and Clinical Immunology 73: 193, 1984Google Scholar
  201. Warner JO, Goldsworthy SJ. Comparative trial of ketotifen and clemastine in childhood seasonal allergic rhinitis and asthma. Research and Clinical Forums 4: 85–95, 1982Google Scholar
  202. Wasek Z, Malinowski R, Plusa T, Kruszewski J. Effect of Zaditen on serum immunoglobulin levels in patients with bronchial asthma. Pneumonologia Polska 53: 81–84, 1985PubMedGoogle Scholar
  203. Watanabe K, Sugai T, Asoh S, Okuno F, Hashimoto Y. Clinical evaluation of ketotifen in patients with atopic dermatitis, urticaria, contact dermatitis and astheatotic dermatitis. Hifu (Skin Research) 30: 419–433, 1988Google Scholar
  204. Wells A, Taylor B. A placebo-controlled trial of ketotifen (HC 20-511, Sandoz) in allergen induced asthma and comparison with disodium cromoglycate. Clinical Allergy 9: 237–240, 1979PubMedCrossRefGoogle Scholar
  205. Welton AF, Hope W, Crowley H, Yaremko B. Comparative mechanism of action of RO 22-3747 (trans-3-[6-(methylthio)-4-oxo-4H-quinazolin-3-yl]-2-propenoic acid), oxatomide and ketotifen. Journal of Allergy and Clinical Immunology 71: 124, 1983CrossRefGoogle Scholar
  206. Wheatley D. Ketotifen in hay fever and allergic rhinitis. Practitioner 228: 685–686, 1984PubMedGoogle Scholar
  207. White MP, MacDonald TH, Garg RA. Ketotifen in the young asthmatic — a double-blind placebo-controlled trial. Journal of International Medical Research 16: 107–113, 1988PubMedGoogle Scholar
  208. Wilhelms O-H. Inhibition profiles of picumast and ketotifen on the in vitro release of prostanoids, slow-reacting substance of anaphylaxis, histamine and enzyme from human leukocytes and rat alveolar macrophages. International Archives of Allergy and Applied Immunology 82: 547–549, 1987PubMedCrossRefGoogle Scholar
  209. Wolf R, Wolf D, Livni E. Pityriasis rosea and ketotifen. Dermatologica 171: 355–356, 1985PubMedCrossRefGoogle Scholar
  210. Wüthrich B, Radielovic P. Zur medikamentösen Bronchialasthma-Prophylaxe. Deutsche Medizinische Wochenschrift 103: 1865–1869, 1978PubMedCrossRefGoogle Scholar
  211. Yoshida H, Niimura M, Ueda H, Imaura S, Yamamoto S, et al. Clinical evaluation of ketotifen syrup on atopic dermatitis: a comparative multicenter double-blind study of ketotifen and clemastine. Annals of Allergy 62: 507–512, 1989PubMedGoogle Scholar
  212. Zanon P, Bruschi C, Cerveri I, Viggiani P, Ferrara R, et al. Protection by ketotifen and disodium cromoglycate against bronchoconstriction induced by inhalation of acetylsalicylic acid. Current Therapeutic Research 38: 785–789, 1985Google Scholar
  213. Zaun H, Peter RU. Wirksamkeit und Verträglichkeit von Loratadin im Vergleich zu Ketotifen bei saisonaler allergischer Rhinitis. Allergologie Jahrgang 13: 29–32, 1990Google Scholar

Copyright information

© Adis International Limited 1990

Authors and Affiliations

  • Susan M. Grant
    • 1
  • Karen L. Goa
    • 1
  • Andrew Fitton
    • 1
  • Eugene M. Sorkin
    • 1
  1. 1.Adis Drug Information ServicesAucklandNew Zealand

Personalised recommendations