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.
Similar content being viewed by others
References
Abbound Al Janabi T (1980) Surgical findings in hydatidiosis after mebendazole therapy. Abstract, Tenth International Congress on Tropical Medicine and Malaria, Manila, p 178
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: 311–319
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: 1435
Alton KB, Patrick JE, McGuire JL (1979) High performance liquid chromatographic assay for the antihelminthic agent mebendazole in human plasma. J Pharm Sci 68: 880–882
Amman R, Akovbiantz A, Eckert J (1979) Chemotherapie der Echinokokkose des Menschen mit Mebendazol (Vermox). Schweiz Med Wochenschr 109: 148–151
Anonymous (1979) Medical treatment for hydatid disease. Br Med J 2: 111
Beard TC, Rickard MD, Goodman HT (1978) Medical treatment for hydatids. Med J Aust 1: 633–635
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: 48–65
Bekhti A, Schaaps JP, Capron A (1977) Treatment of hepatic hydatid disease with mebendazole: preliminary results. Br Med J 2: 1047–1051
Blaschke TF (1977) Protein binding and kinetics of drugs in liver diseases Clin Pharmacokin 2: 32–34
Braithwaite PA (1980) Clinical results obtained in the treatment of hydatid disease with mebendazole in Tasmania. Proceedings, workshop on chemotherapy of larval echinococcosis. Beerse, Belgium
Braithwaite PA (1981) Long term high dose mebendazole for cystic hydatid disease of the liver: Failure in two cases. Aust NZ J Surg 51: 23–27
Braithwaite PA, Lees RF (1981) Vertebral hydatidosis: Radiological appearance. Radiology 140: 763–766
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: 313
Bryceson A (1980) Mebendazole and hydatid disease. Br Med J 280: 796
Campbell WC, McCracken RO, Blair LS (1974) Therapy of hydatid disease. J Am Med Assoc 230: 825
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: 577–584
Eckert J (1980) Experimental chemotherapy of larval Echinococcosis in laboratory Animals. Workshop on chemotherapy of larval echinococcosis, Beerse, Belgium
Eckert J, Barandun G, Pohlenz J (1978) Chemotherapy of echinococcosis in laboratory animals. Schweiz Med Wochenschr 108: 1104–1112
Eckert J, Burkhardt B (1980) Chemotherapy of experimental echinococcosis. Acta Trop 30: 297–300
Gibaldi M, Perrier D (1975) Pharmacokinetics. Marcel Dekker, New York
Goodman HT (1976) Mebendazole. Med J Aust 2: 662
Harris A (1979) Pyrexia and mebendazole. Br Med J 2: 1365
Heath DD, Chevis RA (1974) Mebendazole and hydatid cysts. Lancet 2: 218–219
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: 273–285
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.
Kammerer WS (1980) Treatment of human hydatid disease (Echninococcus granulosus) with a high-dose mebendazole regimen. Workshop on chemotherapy of larval Echinococcosis, Beerse, Belgium
Kammerer WS, Judge DM (1976) Chemotherapy of hydatid disease (Echinococcus granulosus) in mice with Mebendazole and bithionol. Am J Trop Med Hyg 25: 714–717
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: 90–95
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: 141–144
Kern P (1980) Follow up observations of patients with advanced cystic or alveolar echinococcosis with mebendazole. Workshop on chemotherapy of larval Echinococcosis, Beerse, Belgium
Kern P, Dietrich M, Volkmer KJ (1979) Chemotherapy of Echinococcosis with mebendazole. Clinical observations of seven patients. Tropenmed Parasit 30: 65–72
Kovalenko FP (1976) Vyzhivaemost protoskoleksov al'veokokka i ékhinokokka v kishechnike laboratornykh gryzunov. Med Parazitol 45: 350–352
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: 218–219
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, Belgium
Miskovitz PF, Javitt NB (1980) Leukopecia associated with mebendazole therapy of hydatid disease. Am J Trop Med Hyg 29: 1356–1358
Mulhall PP (1980) Treatment of ruptured hydatid cyst of the lung with mebendazole. Br J Dis Chest 74: 306–308
Münst GJ, Karlaganis G, Bircher J (1980) Plasma concentrations of mebendazole during treatment of echinococcosis. Preliminary results. Eur J Clin Pharmacol 17: 375–378
Murray-Lyon IM, Reynolds KW (1979) Complications of mebendazole treatment for hydatid disease. Br Med J 2: 1111–1112
Osborne DR (1980) Mebendazole and hydatid disease. Br Med J 280: 183
Quilici M, Duman H, Rampal M, Alimi JC (1979) Hydatidose: traîtement préoperative par fluromebendazolee. Nouv Presse Med 30: 65–72
Rawlins MD, Coliste P, Bertilsson L, Palmer L (1975) Distribution and elimination kinetics of carbamazepine in man. Eur J Clin Pharmacol 8: 91–96
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: 189–194
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: 175–183
Roberts MS, Denton MJ (1980) Effect of posture and sleep on pharmacokinetics 1. Amoxycillin. Eur J Clin Pharmacol 18: 175–183
Rowland M (1977) Pharmacokinetics in drug metabolism — from microbe to man. Parke DV, Smith RL (eds) Taylor and Francis, London, pp 123–145
Smyth JD (1979) An in vitro approach to taxonomic problems in trematodes and cestodes, especially echinococcus. Parasitology Symposia 1979; 17: 75–101
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: 649–652
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 11087
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, Belgium
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, Belgium
Wilson JF, Davidson M, Rausch RL (1978) A clinical trial of mebendazole in the treatment of alveolar hydatid disease. Am Rev Respir Dis 118: 747–757
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, Belgium
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Braithwaite, P.A., Roberts, M.S., Allan, R.J. et al. Clinical pharmacokinetics of high dose mebendazole in patients treated for cystic hydatid disease. Eur J Clin Pharmacol 22, 161–169 (1982). https://doi.org/10.1007/BF00542462
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00542462