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European Journal of Clinical Pharmacology

, Volume 22, Issue 2, pp 161–169 | Cite as

Clinical pharmacokinetics of high dose mebendazole in patients treated for cystic hydatid disease

  • P. A. Braithwaite
  • M. S. Roberts
  • R. J. Allan
  • T. R. Watson
Originals

Summary

The plasma concentrations of mebendazole and its metabolites have been monitored in twelve patients after receiving a 10 mg/kg dose for cystic hydatid disease. The mebendazole plasma concentration-time profiles differed considerably between patients; elimination half-lives ranged from 2.8–9.0 h, time to peak plasma concentration after dosing ranged from 1.5–7.25 h and peak plasma concentrations ranged from 17.5 to 500 ng/ml. The mean peak plasma concentration of mebendazole after an initial dose (69.5 ng/ml) was lower than found in patients during chronic therapy (137.4 ng/ml). The plasma AUCTs for the major metabolites of mebendazole (methyl 5-(α-hydroxybenzyl)-2-benzimidazole carbamate and 2-amino-5 benzoylbenzimidazole) were about five times the plasma AUCT found for mebendazole in patients on chronic therapy. It is suggested that the slower clearance of these polar metabolites relative to mebendazole results from enterohepatic recycling. Since mebendazole is also highly plasma protein bound, caution should be observed in administering mebendazole to patients with liver disease. Concentrations of mebendazole found in the tissue and cyst material collected from two patients during surgery ranged from 59.5 to 206.6 ng/g wet weight.

Key words

mebendazole hydatid disease Echinococcus granulosus hepatic disease pharmacokinetics 

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References

  1. Abbound Al Janabi T (1980) Surgical findings in hydatidiosis after mebendazole therapy. Abstract, Tenth International Congress on Tropical Medicine and Malaria, Manila, p 178Google Scholar
  2. Allan RJ, Goodman HT, Watson TR (1980) Two high performance liquid chromatographic determinations for mebendazole and its metabolites in human plasma using a rapid Sep Pak C18 extraction. J Chromatogr Biomed Appl 183: 311–319Google Scholar
  3. Al-Moslih MI, Al-Rawas AY, Rassam S, Al-Dabach MA, Al-Janabi TA, Shafik MA, Al-Ani MS (1978) Treatment of hydatidosis. Br Med J 2: 1435Google Scholar
  4. Alton KB, Patrick JE, McGuire JL (1979) High performance liquid chromatographic assay for the antihelminthic agent mebendazole in human plasma. J Pharm Sci 68: 880–882Google Scholar
  5. Amman R, Akovbiantz A, Eckert J (1979) Chemotherapie der Echinokokkose des Menschen mit Mebendazol (Vermox). Schweiz Med Wochenschr 109: 148–151Google Scholar
  6. Anonymous (1979) Medical treatment for hydatid disease. Br Med J 2: 111Google Scholar
  7. Beard TC, Rickard MD, Goodman HT (1978) Medical treatment for hydatids. Med J Aust 1: 633–635Google Scholar
  8. Bekhti A, Nizet M, Capron M, Dessaint JP, et al (1980) Chemotherapy of human hydatid disease with mebendazole. Follow up in 16 cases. Acta Gastroenterol Belgica 1980; 43: 48–65Google Scholar
  9. Bekhti A, Schaaps JP, Capron A (1977) Treatment of hepatic hydatid disease with mebendazole: preliminary results. Br Med J 2: 1047–1051Google Scholar
  10. Blaschke TF (1977) Protein binding and kinetics of drugs in liver diseases Clin Pharmacokin 2: 32–34Google Scholar
  11. Braithwaite PA (1980) Clinical results obtained in the treatment of hydatid disease with mebendazole in Tasmania. Proceedings, workshop on chemotherapy of larval echinococcosis. Beerse, BelgiumGoogle Scholar
  12. Braithwaite PA (1981) Long term high dose mebendazole for cystic hydatid disease of the liver: Failure in two cases. Aust NZ J Surg 51: 23–27Google Scholar
  13. Braithwaite PA, Lees RF (1981) Vertebral hydatidosis: Radiological appearance. Radiology 140: 763–766Google Scholar
  14. Brugmans JP, Thienpont DC, Wijngaarden I, Vanparijis OF, Schuermans VL, Lauwers HL (1971) Mebendazole in enterobiasis. Radiochemical and pilot clinical study in 1,278 subjects. J. Am Med Assoc 217: 313Google Scholar
  15. Bryceson A (1980) Mebendazole and hydatid disease. Br Med J 280: 796Google Scholar
  16. Campbell WC, McCracken RO, Blair LS (1974) Therapy of hydatid disease. J Am Med Assoc 230: 825Google Scholar
  17. Conder GA, Anderson FL, Schantz PM (1980) Immunodiagnostic tests for hydatidosis in sheep: An evaluation of double diffusion, immunoelectrophoresis, indirect hemagglutination, and intradermal tests. J Parasitol 66: 577–584Google Scholar
  18. Eckert J (1980) Experimental chemotherapy of larval Echinococcosis in laboratory Animals. Workshop on chemotherapy of larval echinococcosis, Beerse, BelgiumGoogle Scholar
  19. Eckert J, Barandun G, Pohlenz J (1978) Chemotherapy of echinococcosis in laboratory animals. Schweiz Med Wochenschr 108: 1104–1112Google Scholar
  20. Eckert J, Burkhardt B (1980) Chemotherapy of experimental echinococcosis. Acta Trop 30: 297–300Google Scholar
  21. Gibaldi M, Perrier D (1975) Pharmacokinetics. Marcel Dekker, New YorkGoogle Scholar
  22. Goodman HT (1976) Mebendazole. Med J Aust 2: 662Google Scholar
  23. Harris A (1979) Pyrexia and mebendazole. Br Med J 2: 1365Google Scholar
  24. Heath DD, Chevis RA (1974) Mebendazole and hydatid cysts. Lancet 2: 218–219Google Scholar
  25. Heath DD, Christie MJ, Chevis RAF (1975) The lethal effect of mebendazole on secondary Echinococcus granulosus, cysticerci of Taenia Pisiformis and tetrathyridia of Mesocestoides Corti. Parastiology 70: 273–285Google Scholar
  26. Heykants J, Geuens I, Scheygrond H, Van den Bossche H (1979) Dose dependence and influence of a meal on the absorption and plasma levels of mebendazole in volunteers. Janssen Pharmaceutica Clinical research report R17889/18 June 1979. Beerse, Belgium.Google Scholar
  27. Kammerer WS (1980) Treatment of human hydatid disease (Echninococcus granulosus) with a high-dose mebendazole regimen. Workshop on chemotherapy of larval Echinococcosis, Beerse, BelgiumGoogle Scholar
  28. Kammerer WS, Judge DM (1976) Chemotherapy of hydatid disease (Echinococcus granulosus) in mice with Mebendazole and bithionol. Am J Trop Med Hyg 25: 714–717Google Scholar
  29. Kammerer WS, Perez-Esaudi MV (1975) Chemotherapy of experimental Echinococcus granulosus infection. Trials in CF 1 mice and jirds (Meroines unguliculatus). Am J Trop Med Hyg 24: 90–95Google Scholar
  30. Karlaganis G, Münst GJ, Bicher J (1979) High pressure liquid chromatographic determination of the antihelminthic drug mebendazole in plasma. J High Resolution Chromatogr. Chromatogr Commun 2: 141–144Google Scholar
  31. Kern P (1980) Follow up observations of patients with advanced cystic or alveolar echinococcosis with mebendazole. Workshop on chemotherapy of larval Echinococcosis, Beerse, BelgiumGoogle Scholar
  32. Kern P, Dietrich M, Volkmer KJ (1979) Chemotherapy of Echinococcosis with mebendazole. Clinical observations of seven patients. Tropenmed Parasit 30: 65–72Google Scholar
  33. Kovalenko FP (1976) Vyzhivaemost protoskoleksov al'veokokka i ékhinokokka v kishechnike laboratornykh gryzunov. Med Parazitol 45: 350–352Google Scholar
  34. Krotov AI, Tchernaev AI, Kovalenko FB, Bajandino DG, et al (1974) (Experimental therapy of Alveococcosis, 11. Effectivity of some defensive remedies against alveococcosis of laboratory animals.) (Russian). Med Parazitol 2: 218–219Google Scholar
  35. Michiels M, Hendriks R, Thijssen J, Heykants J (1978) A sensitive radioimmunoassay for mebendazole and flubendazole. Janssen Pharmaceutica Preclinical Research Reports R17635/11 and R17889/9, November 1978, Beerse, BelgiumGoogle Scholar
  36. Miskovitz PF, Javitt NB (1980) Leukopecia associated with mebendazole therapy of hydatid disease. Am J Trop Med Hyg 29: 1356–1358Google Scholar
  37. Mulhall PP (1980) Treatment of ruptured hydatid cyst of the lung with mebendazole. Br J Dis Chest 74: 306–308Google Scholar
  38. Münst GJ, Karlaganis G, Bircher J (1980) Plasma concentrations of mebendazole during treatment of echinococcosis. Preliminary results. Eur J Clin Pharmacol 17: 375–378Google Scholar
  39. Murray-Lyon IM, Reynolds KW (1979) Complications of mebendazole treatment for hydatid disease. Br Med J 2: 1111–1112Google Scholar
  40. Osborne DR (1980) Mebendazole and hydatid disease. Br Med J 280: 183Google Scholar
  41. Quilici M, Duman H, Rampal M, Alimi JC (1979) Hydatidose: traîtement préoperative par fluromebendazolee. Nouv Presse Med 30: 65–72Google Scholar
  42. Rawlins MD, Coliste P, Bertilsson L, Palmer L (1975) Distribution and elimination kinetics of carbamazepine in man. Eur J Clin Pharmacol 8: 91–96Google Scholar
  43. Reisen IL, Rabito CA, Rotunno CA, Cereijido M (1977) The permeability of the membranes of experimental secondary cysts of Echinococcus granulosus to C14 mebendazole. Int J Parasitol 7: 189–194Google Scholar
  44. Ritschel WA, Hammer GV (1980) Prediction of the volume of distribution from in vitro data and use for estimating the absolute extent of absorption. Int J Clin Pharmacol Ther Toxicol 18: 175–183Google Scholar
  45. Roberts MS, Denton MJ (1980) Effect of posture and sleep on pharmacokinetics 1. Amoxycillin. Eur J Clin Pharmacol 18: 175–183Google Scholar
  46. Rowland M (1977) Pharmacokinetics in drug metabolism — from microbe to man. Parke DV, Smith RL (eds) Taylor and Francis, London, pp 123–145Google Scholar
  47. Smyth JD (1979) An in vitro approach to taxonomic problems in trematodes and cestodes, especially echinococcus. Parasitology Symposia 1979; 17: 75–101Google Scholar
  48. Smyth JD, Barrett NJ (1980) Procedures for testing the viability of human hydatid cysts following surgical removal, especially after chemotherapy. R Soc Trop Med Hyg 74: 649–652Google Scholar
  49. Vanparijs OF, Hermans L, Thienpont D (1976) Anthelmintic activity of mebendazole on larval stages of Echinococcus granulosus in mice. Janssen Res Prod Inf Service N 11087Google Scholar
  50. Van Wijngaarden I (1971) Excretion and metabolism of 14C labelled mebendazole in rats and men. Janssen Pharmaceutica, Biological research reports R17635/2 January 1971, Beerse, BelgiumGoogle Scholar
  51. Wilson JF (1980) Alveolar hydatid disease: a review of clinical features of 33 indigenous cases of Echinococcus multilocularis infection in Alaskan Eskimos. Workshop: Chemotherapy of larval Echinococcosis, Beerse, BelgiumGoogle Scholar
  52. Wilson JF, Davidson M, Rausch RL (1978) A clinical trial of mebendazole in the treatment of alveolar hydatid disease. Am Rev Respir Dis 118: 747–757Google Scholar
  53. Wynants J, Hendrickx J, Heykants J (1975) A high performance liquid chromatographic assay method for mebendazole in plasma and tissues in the 0.1–0.01 range. Janssen Pharmaceutica Biological Research Report R17635/6, January 1975, Beerse, BelgiumGoogle Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • P. A. Braithwaite
    • 1
    • 4
  • M. S. Roberts
    • 2
  • R. J. Allan
    • 3
  • T. R. Watson
    • 3
  1. 1.Department of Surgery, Faculty of MedicineUniversity of TasmaniaHobartAustralia
  2. 2.School of Pharmacy, Faculty of MedicineUniversity of TasmaniaSandy BayAustralia
  3. 3.Department of PharmacyUniversity of SydneyAustralia
  4. 4.Department of SurgeryUniversity of Melbourne Royal Melbourne HospitalParkvilleAustralia

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