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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.
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.
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.
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.
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.
KeywordsAsthma Atopic Dermatitis Cromoglycate Peak Expiratory Flow Sodium Cromoglycate
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- 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
- Asrilant M, Zelazco M. Actividad profilactica del ketotifeno en el asma bronquial extrinseca. Prensa Médica Argentina 69: 548–556, 1982Google Scholar
- Bakran Jr I, Cvoriscec B, Durakovic Z. Ketotifen versus disodium cromoglycate (DSCG) in allergic bronchial asthma. Respiration 42 (Suppl. 1): 115–116, 1981Google Scholar
- 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
- Baronti A, Vibelli C. Ketotifen in skin-test-positive perennial asthma. Current Therapeutic Research 33: 401–407, 1983Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Dorward AJ, Patel KR. Inhaled ketotifen in exercise-induced asthma — a negative report. European Journal of Respiratory Disease 67: 378–380, 1985Google Scholar
- 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
- 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
- Furlan J, Suskovic S, Gashi A. Preventive effect of ketotifen on bronchoconstriction induced by food allergens. Respiration 46 (Suppl.): 16, 1984Google Scholar
- 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
- 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
- Haustein U-F. Ketotifen hemmt Juckreiz und Tumor-progression bei Neurofibromatose. Dermatologische Monatsschrift 175: 581–584, 1989Google Scholar
- Herjavecz I, Böszörmeny-Nagy G. Medikamentöse Prophylaxe bei allergischem Asthma bronchiale. Zeitschrift fur Allergologie Medizin 58: 1425–1428, 1982Google Scholar
- 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
- Hruskovic I. Evaluation of prohylactic treatment of asthma in children: a double-blind controlled trial. Allergologia et Immunopathologia 88: 476, 1980Google Scholar
- 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
- 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
- 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
- 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
- Kennedy GR. Metabolism and pharmacokinetics of ketotifen in children. Research and Clinical Forums 4: 17–20, 1982Google Scholar
- 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
- 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
- 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
- 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
- León G, Arellano I. Tolerancia y eficacia del ketotifeno en ninos con dermatitis atöpica. Dermatologia (Méx.) 33: 153–160, 1989Google Scholar
- 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
- López JGH. Ketotifeno en la profilaxis del asma infantil. Ensayo clinico controlado. Allergologia et Immunopathologia 13: 1–7, 1985Google Scholar
- 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
- 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
- Maclay WP, Crowder D. Post-marketing surveillance of ketotifen (Zaditen®): an interim report. Research and Clinical Forums 4: 51–64, 1982Google Scholar
- Maclay WP, Crowder D. Report on Zaditen postmarketing surveillance. Progress in Respiratory Research 20: 182–190, 1985Google Scholar
- 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
- 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
- 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
- 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
- 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
- Molkhou P, Dupont C. Ketotifen treatment of atopic dermatitis and other food allergy diseases. Allergy 44 (Suppl.): 117–123, 1989Google Scholar
- 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
- Nakayama Y, Tsukamoto T. Long term trial of oral ketotifen-MR on adults with bronchial asthma. Shingaku to Rinsho 38: 1423–1432, 1989Google Scholar
- Neijens HJ, Knol K. Oral prophylactic treatment in wheezy infants. Immunology and Allergy Practice 10: 17–23, 1988Google Scholar
- 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
- 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
- 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
- Pastorello E, Zanussi C. Ketotifen in the long-term treatment of aspirin-intolerant patients. Progress in Respiratory Research 19: 401–405, 1985Google Scholar
- Phanuphak P, Locharernkul C. Double-blind, placebo-controlled study of ketotifen in chronic urticaria. Journal of Allergy and Clinical Immunology 77: 187, 1986Google Scholar
- 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
- 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
- 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
- Rebmann H. Ketotifen in der Kombinationstherapie des kindlichen Asthma bronchiale: Einfluss auf Lungenfunktionsparameter für kleine Atemwege. Allergologie 10: 60–63, 1987Google Scholar
- Reid JJ. Double-blind trial of ketotifen in childhood chronic cough and wheeze. Immunology and Allergy Practice li: 143–150, 1989Google Scholar
- 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
- 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
- Rokicka-Milewska R, Berek-Pyzik B. Ketotifen use in infants with atopy with recurrent obturative bronchitis. Materia Medica Polona 18: 101–103, 1986Google Scholar
- 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
- Sakuma Y, Mita H. Topical ketotifen suppressed ocular provocation for Japanese cedar pollinosis. Japanese Journal of Clinical Ophthalmology 43: 1251–1254, 1989Google Scholar
- 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
- 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
- Schubotz R. Long-term study of the protective effect of ketotifen in asthmatic patients. International Congress Series 523: 40–46, 1979Google Scholar
- Senna GE, Andri G, Caviglia A, Andri L. Uso del chetotifene nell’orticaria cronica. Dermatologie Clinics 8: 41–45, 1988Google Scholar
- 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
- 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
- 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
- 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
- Tholen St, Dieterich HA. Terfenadin versus Ketotifen bei Kindern mit atopischer Dermatitis. Allergologie 12: 60–63, 1989Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Zaun H, Peter RU. Wirksamkeit und Verträglichkeit von Loratadin im Vergleich zu Ketotifen bei saisonaler allergischer Rhinitis. Allergologie Jahrgang 13: 29–32, 1990Google Scholar