Clinical Pharmacokinetics

, Volume 7, Issue 6, pp 465–489 | Cite as

Clinical Pharmacokinetics of Oral Activated Charcoal in Acute Intoxications

  • Pertti J. Neuvonen
Article

Summary

Activated charcoal has the ability to adsorb a wide variety of substances onto its surface. This property can be applied in preventing the absorption of various drugs and toxins from the gastrointestinal tract and in some cases to increase their rate of elimination. In vitro, the extent of adsorption depends mainly on the relative amounts of the charcoal and the drug ingested, but the quality and formulation of the activated charcoal, as well as other factors such as the pH of the incubation medium also have an effect. Under optimum conditions the adsorption to charcoal is a rapid process but desorption from charcoal is possible due, for example, to competition by other substances or to changes in pH.

In acute poisonings the most important determinants of the efficacy of activated charcoal are the delay in the administration and the amount of activated charcoal given. Activated charcoal should be given as a water suspension as soon as possible, preferably within 30 minutes of the ingestion of the toxic agent. However, in acute intoxications the absorption of drugs may be considerably delayed and thus charcoal may be effective when administered 24 hours after drug ingestion. At a constant charcoal-drug ratio, the adsorption capacity of charcoal increases with increasing doses because the competitive effect of gastrointestinal contents diminishes. Thus the amount of charcoal should be as high as feasible, i.e. about 50 to 100g in adults. This amount is able to adsorb lethal doses of many drugs. Significant desorption from charcoal and subsequent systemic absorption of a drug is possible if inadequate amounts of charcoal are used. The adsorption to charcoal is more complete in poisonings with potent drugs, i.e. where the charcoal-drug ratio is high (e.g. digitalis glycosides, tricyclic antidepressants, etc.). With some drugs the adsorption capacity may be exceeded, e.g. in aspirin poisonings, but even in these cases the charcoal may adsorb that fraction of the drug which is dissolved in the gastrointestinal fluids.

In experimental studies, the efficacy of charcoal in preventing systemic absorption of many drugs has been of the same order or even better than that of emesis, but in certain poisonings the efficacy of charcoal is inadequate, e.g. in those caused by ethanol, methanol or iron salts. Charcoal is rather ineffective and may even be contraindicated in poisonings caused by caustic alkalis or acids. Charcoal is non-toxic but, if administered too rapidly, patients may vomit.

Some drugs and toxic agents have a long elimination half-life and are excreted into the gastrointestinal tract and then reabsorbed. With such agents multiple oral doses of activated charcoal, e.g. 20g every 6 hours for 1 or 2 days, can accelerate their elimination and shorten the duration of intoxication.

There are considerable differences between various countries in the availability of activated charcoal and even between various medical centres in their willingness to use charcoal. Activated charcoal should be a part of the first-aid kit both at home and at work to avoid unnecessary delays in administration.

Keywords

Charcoal Digoxin Activate Charcoal Tolbutamide Dapsone 

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References

  1. Abdallah, A.H. and Tye, A.: A comparison of efficacy of emetic drags and stomach lavage. American Journal of Diseases of Children 113: 571–575 (1967).PubMedGoogle Scholar
  2. Alvan, G.: Effect of activated charcoal on plasma levels of nortriptyline after single doses in man. European Journal of Clinical Pharmacology 5: 236–238 (1973).CrossRefGoogle Scholar
  3. Andersen, A.H.: Experimental studies on the pharmacology of activated charcoal. I. Adsorption power in aqueous solutions. Acta Pharmacologica 2: 69–78 (1946).CrossRefGoogle Scholar
  4. Andersen, A.H.: Experimental studies on the pharmacology of activated charcoal. II. The effect of pH on the adsorption by charcoal from aqueous solutions. Acta Pharmacologica 3: 199–218 (1947).CrossRefGoogle Scholar
  5. Andersen, A.H.: Experimental studies on the pharmacology of activated charcoal. III. Adsorption from gastro-intestinal contents. Acta Pharmacologica 4: 275–284 (1948a).CrossRefGoogle Scholar
  6. Andersen, A.H.: Pharmacology of activated charcoal. IV. Adsorption of allylisopropylbarbituric acid in vivo. Acta Pharmacologica 4: 379–388 (1948b).CrossRefGoogle Scholar
  7. Andersen, A.H.: Medicinal charcoal in the treatment of poisoning. Treatment of experimental poisoning in pigs. Ugeskrift fur Laeger 135: 797–801 (1973).Google Scholar
  8. Arnold, F.J.; Hodges, J.B.; Barta, R.A.; Spector, S.; Sunshine, I. and Wedgwood, R.J.: Evaluation of the efficacy of lavage and induced emesis in treatment of salicylate poisoning. Pediatrics 23: 286–301 (1959).PubMedGoogle Scholar
  9. Bainbridge, C.A.; Kelly, E.L. and Walking, W.D.: In vitro adsorption of acetaminophen onto activated charcoal. Journal of Pharmaceutical Sciences 4: 480–483 (1977).CrossRefGoogle Scholar
  10. Belz, G.G.: Plasma concentrations of intravenous β-methyl di-goxin with and without oral charcoal. Klinische Wochenschrift 52: 749–750 (1974).PubMedCrossRefGoogle Scholar
  11. Belz, G.G. and Bader, H.: Effect of oral charcoal on plasma levels of intravenous methyl proscillaridin. Klinische Wochenschrift 52: 1134–1135 (1974).PubMedCrossRefGoogle Scholar
  12. Boehm, J.J. and Oppenheim, R.C.: An in vitro study of the adsorption of various drags by activated charcoal. Australian Journal of Pharmaceutical Sciences 4: 107–111 (1977).Google Scholar
  13. Boxer, L.; Anderson, F.P. and Rowe, S.S.: Comparison of ipecac-induced emesis with gastric lavage in the treatment of acute salicylate ingestion. Pediatric Pharmacology and Therapeutics 5: 800–803 (1969).Google Scholar
  14. Boyd, J.R.: Drag Facts and Comparisons, p. 1839 (Lippincott, Philadelphia-Toronto 1982).Google Scholar
  15. Braithwaite, R.A.; Crome, P. and Dawling, S.: The in vitro and in vivo evaluation of activated charcoal as an adsorbent for tricyclic antidepressants. British Journal of Clinical Pharmacology 5: 369 (1978).Google Scholar
  16. Caldwell, J.H.; Caldwell, P.B.; Murphy, J.W. and Beachler, C.W.: Intestinal secretion of digoxin in the rat. Augmentation by feeding activated charcoal. Naunyn-Schmiedeberg’s Archives of Pharmacology 312: 271–275 (1980).PubMedCrossRefGoogle Scholar
  17. Caldwell, J.H. and Cline, CT.: Biliary excretion of digoxin in man. Clinical Pharmacology and Therapeutics 19: 410–415 (1976).PubMedGoogle Scholar
  18. Caldwell, J.H. and Greenberger, N.J.: Interruption of the entero-hepatic circulation of digitoxin by cholestyramine: I. Protection against lethal digitoxin intoxication. Journal of Clinical Investigation 50: 2626–2637 (1971).PubMedCrossRefGoogle Scholar
  19. Calvert, W.E.; Corby, D.G.; Herbertson, L.M. and Decker, W.J.: Orally administered activated charcoal: acceptance by children. Journal of the American Medical Association 215: 641 (1971).PubMedCrossRefGoogle Scholar
  20. Carruthers, S.G. and Dujovne, C.A.: Cholestyramine and digitoxin elimination. Clinical Pharmacology and Therapeutics 39: 92–94 (1979).Google Scholar
  21. Chaput de Saintonge, D.M. and Herxheimer, A: Activated charcoal impairs propantheline absorption. European Journal of Clinical Pharmacology 4: 52–53 (1971).PubMedCrossRefGoogle Scholar
  22. Chernish, S.M.; Wolen, R.L. and Rodda, B.E.: Adsorption of propoxyphene hydrochloride by activated charcoal. Clinical Toxicology 5: 317–329 (1972).PubMedCrossRefGoogle Scholar
  23. Chin, L.; Picchioni, A.L.; Bourn, W.M. and Laird, H.E.: Optimal antidotal dose of activated charcoal. Toxicology and Applied Pharmacology 26: 103–108 (1973).PubMedCrossRefGoogle Scholar
  24. Chin, L.; Picchioni, A.L. and Duplisse, B.R.: The action of activated charcoal on poisons in the digestive tract. Toxicology and Applied Pharmacology 16: 786–799 (1970).PubMedCrossRefGoogle Scholar
  25. Cooney, D.O.: A ‘superactive’ charcoal for antidotal use in poisonings. Clinical Toxicology 11: 387–390 (1977a).PubMedCrossRefGoogle Scholar
  26. Cooney, D.O.: The treatment of ethylene glycol poisoning with activated charcoal. IRCS Medical Sciences 5: 265 (1977b).Google Scholar
  27. Cooney, D.O.: In vitro evidence for ipecac inactivation by activated charcoal. Journal of Pharmaceutical Sciences 67: 426–427 (1978).PubMedCrossRefGoogle Scholar
  28. Cooney, D.O.: Activated Charcoal (Marcel Dekker, Inc., New York 1980).Google Scholar
  29. Corby, D.G. and Decker, W.J.: Management of acute poisoning with activated charcoal. Pediatrics 54: 324–329 (1974).PubMedGoogle Scholar
  30. Corby, D.G.; Decker, W.J.; Moran, M.J. and Payne, C.E.: Clinical comparison of pharmacologic emetics in children. Pediatrics 4: 361–364 (1968).Google Scholar
  31. Corby, D.G.; Lisciandro, R.C.; Lehman, R.H. and Decker, W.J.: The efficiency of methods used to evacuate the stomach after acute ingestions. Pediatrics 5: 871–874 (1967).Google Scholar
  32. Crome, P.; Dawling, S.; Braithwaite, R.A.; Masters, J. and Walkey, R.: Effect of activated charcoal on absorption of nortriptyline. Lancet 2: 1203–1205 (1977).PubMedCrossRefGoogle Scholar
  33. Dawling, S.; Crome, P. and Braithwaite, R.: Effect of delayed administration of activated charcoal on nortriptyline absorption. European Journal of Clinical Pharmacology 14: 445–447 (1978).PubMedCrossRefGoogle Scholar
  34. Decker, W.J.; Combs, H.F. and Corby, D.G.: Adsorption of drug and poison by activated charcoal. Toxicology and Applied Pharmacology 13: 454–469 (1968).PubMedCrossRefGoogle Scholar
  35. Decker, W.J. and Corby, D.G.: Activated charcoal adsorbs aflatoxin B1. Veterinary and Human Toxicology 22: 388–389 (1980).PubMedGoogle Scholar
  36. Decker, W.J.; Shpall, R.A.; Corby, D.G.; Combs, H.F. and Payne, C.E.: Inhibition of aspirin absorption by activated charcoal and apomorphine. Clinical Pharmacology and Therapeutics 4: 710–713 (1969).Google Scholar
  37. Doherty, J.E.; Flanigan, W.J.; Murphy, M.L..; Bulloch, R.T.; Dalrymple, G.L.; Beard, D.W. and Perkins, W.H.: Tritiated di-goxin. XIV. Enterohepatic circulation absorption, and excretion studies in’human volunteers. Circulation 42: 867–873 (1970).PubMedCrossRefGoogle Scholar
  38. Dordoni, P.; Willson, R.A.; Thompson, R.P.H. and Williams, R.: Reduction of absorption of paracetamol by activated charcoal and cholestyramine: a possible therapeutic measure. British Medical Journal 3: 86–87 (1973).PubMedCrossRefGoogle Scholar
  39. Dozzi, A.M.; Leversha, A. and Stewart, N.F.: Comparison of activated charcoals. Australian Journal of Hospital Pharmacy 4: 40–41 (1974).Google Scholar
  40. Du Souich, P.; Caillé, G. and Larochelle, P.: Reduction of nadolol plasma half-life by activated charcoal and antibiotics in man. Clinical Pharmacology and Therapeutics 31: 222 (1982).Google Scholar
  41. Fiser, R.H.; Maetz, H.M.; Treuting, J.J. and Decker, W.J.: Activated charcoal in barbiturate and glutethimide poisoning of the dog. Pediatric Pharmacology and Therapeutics 6: 1045–1047 (1971).Google Scholar
  42. Garattini, S.: Hepatic toxicity with TCDD. Presented at National Academy of Sciences, Workshop on Plans of Clinical and Epidemiological Follow-up after Areawide Chemical Contamination, Washington D.C. (March 19, 1980).Google Scholar
  43. Gilman, A.G.; Goodman, L.S. and Gilman, A. (Eds): The Pharmacological Basis of Therapeutics (6th ed.) p.954 (Macmillan, New York 1980).Google Scholar
  44. Goldberg, M.J. and Berlinger, W.G.: Treatment of phenobarbital overdose with activated charcoal. Journal of the American Medical Association 247: 2400–2401 (1982).PubMedCrossRefGoogle Scholar
  45. Goodman, L.S. and Gilman, A. (Eds): The Pharmacological Basis of Therapeutics (4th ed.) p.990 (Macmillan, New York 1970).Google Scholar
  46. Goodman, L.S. and Gilman, A. (Eds): The Pharmacological Basis of Therapeutics (5th ed.) p.949 (Macmillan, New York 1975).Google Scholar
  47. Härtel, G.; Manninen, V. and Reissel, P.: Treatment of digoxin intoxication. Lancet 2: 158 (1973).PubMedCrossRefGoogle Scholar
  48. Hayden, J.W. and Comstock, E.G.: Use of activated charcoal in acute poisoning. Clinical Toxicology 8: 515–533 (1975).PubMedCrossRefGoogle Scholar
  49. Helliwell, M. and Berry, D.: Theophylline absorption by effervescent activated charcoal (’Medicoal’). Journal of International Medical Research 9: 222–225 (1981).PubMedGoogle Scholar
  50. Holt, L.E. Jr and Holz, P.H.: The black bottle. Journal of Pediatrics 63: 306–314 (1963).PubMedCrossRefGoogle Scholar
  51. Jackson, J.E.; Picchioni, A.L. and Chin, L.: Contraindications for activated charcoal use. Annals of Emergency Medicine 9: 599 (1980).PubMedCrossRefGoogle Scholar
  52. Karlsson, B. and Noren, L.: Ipecacuanha and copper sulphate as emetics in intoxication in children. Acta Paediatrica Scandinavica 54: 331–335 (1965).PubMedCrossRefGoogle Scholar
  53. Klein-Schwartz, W. and Oderda, G.: Adsorption of oral antidotes for acetaminophen poisoning (methionine and N-acetylcysteine) by activated charcoal. Paper presented to 1980 National Poison Center Network Annual Symposium, Pittsburgh, Penn. (June 10, 1980).Google Scholar
  54. Korttila, K.; Mattila, M.J. and Linnoila, M.: Prolonged recovery after diazepam sedation: the influence of food, charcoal ingestion and injection rate on the effects of intravenous diazepam. British Journal of Anaesthesia 48: 333–340 (1976).PubMedCrossRefGoogle Scholar
  55. Laass, W.: Zur Eignung von Carbo medicinalis für die Behandlung akuter oraler Vergiftungen mit organischen Lösungsmitteln. Pharmazie 29: 728 (1974).PubMedGoogle Scholar
  56. Laass, W.: Therapy of acute oral poisonings by organic solvents: treatment by activated charcoal in combination with laxatives. Archives of Toxicology 4 (Suppl.): 406–409 (1980).PubMedCrossRefGoogle Scholar
  57. Levy, G. and Houston, J.B.: Effect of activated charcoal on acetaminophen absorption. Pediatrics 3: 432–435 (1976).Google Scholar
  58. Levy, G. and Tsuchiya, T.: Effect of activated charcoal on aspirin absorption in man. Clinical Pharmacology and Therapeutics 13: 317–322 (1972).PubMedGoogle Scholar
  59. Lipscomb, D.J. and Widdop, B.: Studies with activated charcoal in the treatment of drug overdosage using the pig as an animal model. Archives of Toxicology 34: 37–46 (1975).PubMedCrossRefGoogle Scholar
  60. Manoguerra, A.S. and Krenzelok, E.P.: Rapid emesis from high-dose ipecac syrup in adults and children intoxicated with antiemetics or other drugs. American Journal of Hospital Pharmacy 35: 1360–1362 (1978).PubMedGoogle Scholar
  61. Mayersohn, M.; Perrier, D. and Picchioni, A.L.: Evaluation of a charcoal-sorbitol mixture as an antidote for oral aspirin over-dose. Clinical Toxicology 11: 561–567 (1977).PubMedCrossRefGoogle Scholar
  62. Neuvonen, P.J. and Alanen, T.: Does ethanol decrease drug adsorption to activated charcoal? Second Finnish Symposium on the Biological and Medical Effects of Alcohol (Abstracts), Helsinki, Finland (October 8, 1981).Google Scholar
  63. Neuvonen, P.J.; Elfving, S.M. and Elonen, E.: Reduction of absorption of digoxin, Phenytoin and aspirin by activated charcoal in man. European Journal of Clinical Pharmacology 13: 213–218 (1978).PubMedCrossRefGoogle Scholar
  64. Neuvonen, P.J. and Elonen, E.: Effect of activated charcoal on absorption and elimination of phenobarbitone, carbamazepine and phenylbutazone in man. European Journal of Clinical Pharmacology 17: 51–57 (1980).PubMedCrossRefGoogle Scholar
  65. Neuvonen, P.J.; Elonen, E. and Mattila, M.J.: Oral activated charcoal and dapsone elimination. Clinical Pharmacology and Therapeutics 6: 823–827 (1980).Google Scholar
  66. Neuvonen, P.J.; Tokola, O. and Vartiainen, M.: Comparison of activated charcoal and ipecac syrup in prevention of drug absorption. Clinical Pharmacology and Therapeutics 31: 255–256 (1982a).Google Scholar
  67. Neuvonen, P.J.; Kannisto, H.; Alanen, T. and Hirvisalo, E.L.: Effect of activated charcoal on the absorption of tolbutamide and valproate in man. (Abstract) p.142 Joint Meeting of the British and Scandinavian Pharmacological Societies, 4–6 July 1982, Stockholm (1982b).Google Scholar
  68. North, D.S.; Peterson, R.G. and Krenzelok, E.P.: Effect of activated charcoal administration on acetylcysteine serum levels in humans. American Journal of Hospital Pharmacy 38: 1022–1024 (1981a).PubMedGoogle Scholar
  69. North, D.S.; Thompson, J.D. and Peterson, C.D.: Effect of activated charcoal on ethanol blood levels in dogs. American Journal of Hospital Pharmacy 38: 864–866 (1981b).PubMedGoogle Scholar
  70. Okonek, S.; Setyadharma, H.; Borchert, A. and Krienke, E.G.: Activated charcoal is as effective as Fuller’s earth or bentonite in paraquat poisoning. Klinische Wochenschrift 60: 207–210 (1982).PubMedCrossRefGoogle Scholar
  71. Otto, U. and Stenberg, B.: Drug adsorption properties of different activated charcoal dosage forms in vitro and in man. Svensk Farmaceutisk Tidskrift 77: 613–615 (1973).Google Scholar
  72. Phansalkar, S.V. and Holt, I.E. Jr.: Observations on the immediate treatment of poisoning. Journal of Pediatrics 5: 683–685 (1968).Google Scholar
  73. Picchioni, A.L.: Activated charcoal, a neglected antidote. Pediatric Clinics of North America 17: 535–543 (1970).PubMedGoogle Scholar
  74. Picchioni, A.L.; Chin, L. and Laird, H.E.: Activated charcoal preparations — relative antidotal efficacy. Clinical Toxicology 7: 97–108 (1974).PubMedCrossRefGoogle Scholar
  75. Pond, S.; Jacobs, M.; Marks, J.; Garner, J.; Goldschlager, N. and Hansen, P.: Treatment of digitoxin overdose with oral activated charcoal. Lancet 2: 1177–1178 (1981).PubMedCrossRefGoogle Scholar
  76. Prescott, L.F.: Drug overdosage and poisoning; in Avery (Ed.) Drug Treatment (2nd ed.), pp.263–282 (ADIS Press, Sydney 1980).Google Scholar
  77. Prescott, L.F.; Park, J.; Ballantyne, A.; Adriaenssens, P. and Proudfoot, A.T.: Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet 2: 432–434 (1977).PubMedCrossRefGoogle Scholar
  78. Rauws, A.G. and van Noordwijk, J.: Activated charcoal in tricyclic drug overdoses. British Medical Journal 4: 298 (1972).CrossRefGoogle Scholar
  79. Rauws, A.G. and Olling, M.: Treatment of experimental imipramine and desipramine poisoning in the rat. Archives of Toxicology 35: 97–106 (1976).PubMedCrossRefGoogle Scholar
  80. Robertson, W.O.: Syrup of ipecac — a slow or fast emetic?. American Journal of Diseases of Children 103: 136–139 (1962).PubMedGoogle Scholar
  81. Rosenberg, J.; Benowitz, N.L. and Pond, S.: Pharmacokinetics of drug overdose. Clinical Pharmacokinetics 6: 161–192 (1981).PubMedCrossRefGoogle Scholar
  82. Scheinin, M.; Virtanen, R.; Iisalo, E. and Salonen, J.S.: Effect of activated charcoal on the pharmacokinetics of doxepin. Naunyn-Schmiedeberg’s Archives of Pharmacology 313 (Suppl.): 223 (1980).Google Scholar
  83. Sellers, E.M.; Khuow, V. and Dolman, L.: Comparative drug adsorption by activated charcoal. Journal of Pharmaceutical Sciences 11: 1640–1641 (1977).CrossRefGoogle Scholar
  84. Sintek, C.; Hendeles, L. and Weinberger, M.: Activated charcoal adsorption of theophylline in vitro. Drug Intelligence and Clinical Pharmacy 12: 158 (1978).Google Scholar
  85. Sintek, C.; Hendeles, L. and Weinberger, M.: Inhibition of theophylline absorption by activated charcoal. Journal of Pediatrics 94: 314–316 (1979).PubMedCrossRefGoogle Scholar
  86. Sketris, I.S.; Mowry, J.B.; Czajka, P.A.; Anderson, W.H. and Stafford, D.T.: Saline catharsis: Effect on aspirin bioavailability in combination with activated charcoal. Journal of Clinical Pharmacology 22: 59–64 (1982).PubMedGoogle Scholar
  87. Sorby, D.L.: Effect of adsorbents on drug absorption. I. Modification of promazine absorption by activated attapulgite and activated charcoal. Journal of Pharmaceutical Sciences 5: 677–683 (1965).CrossRefGoogle Scholar
  88. Szabuniewicz, M.; Bailey, E.M. and Wiersig, D.O.: A new regimen for the treatment of ethylene glycol poisoning. IRCS Medical Science 3: 102 (1975).Google Scholar
  89. Takki, S.; Gambertoglio, J.G.; Honda, D.H. and Tozer, T.N.: Pharmacokinetic evaluation of hemodialysis in acute drug overdose. Journal of Pharmacokinetics and Biopharmaceutics 5: 427–442 (1978).Google Scholar
  90. Todd, P.J.; Sills, J.A.; Harris, F. and Cowen, J.M.: Problems with overdoses of sustained-release aspirin. Lancet 1: 777 (1981).PubMedCrossRefGoogle Scholar
  91. Tsuchiya, T. and Levy, G.: Drug adsorption efficacy of commercial activated charcoal tablets in vitro and in man. Journal of Pharmaceutical Sciences 61: 624–625 (1972a).PubMedCrossRefGoogle Scholar
  92. Tsuchiya, T. and Levy, G.: Relationship between effect of activated charcoal on drug absorption in man and its drug adsorption characteristics in vitro. Journal of Pharmaceutical Sciences 61: 586–589 (1972b).PubMedCrossRefGoogle Scholar
  93. Venho, V.M.K..; Salonen, R.O. and Mattila, M.J.: Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal. European Journal of Clinical Pharmacology 14: 277–280 (1978).PubMedCrossRefGoogle Scholar
  94. Volans, G.N.: General principles of treatment; in Vale and Meredith (Eds) Poisoning; Diagnosis and Treatment, pp.26–32 (Update Books, London, Dordrecht, Boston 1981).CrossRefGoogle Scholar
  95. Yatzidis, H.: Activated charcoal rediscovered. British Medical Journal 7: 51 (1972).CrossRefGoogle Scholar

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© ADIS Press Australasia Pty Ltd (Inc. NSW). 1982

Authors and Affiliations

  • Pertti J. Neuvonen
    • 1
  1. 1.Department of Clinical PharmacologyUniversity of Helsinki and University Central HospitalHelsinki 25Finland

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