Lack of effect of haemodialysis on mebendazole kinetics: Studies in a patient with echinococcosis and renal failure

Allgayer, H.; Zähringer, J.; Bircher, J

doi:10.1007/bf00544053

Cited by 5 publications

(1 citation statement)

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“…This conclusion has, however, been ques-75 tioned (Luder et al 1986). No reduction in mebendazole dose is warranted in patients with impairment of renal function (Allgayer et al 1985) but, because of limited experience with the use of the drug in children under 2 years of age, it is not currently recommended for this group. There are no reports of the transfer ofmebendazole into breast milk, but mebendazole has been reported to be embryotoxic and teratogenic in pregnant rats and for this reason it is contraindicated in pregnancy.…”

Section: Clinical Considerationsmentioning

confidence: 95%

Clinical Pharmacokinetics of Anthelmintic Drugs

Edwards

Breckenridge

1988

Clinical Pharmacokinetics

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A rational strategy for chemotherapy demands that dosage schedules be based on an adequate knowledge of clinical and biochemical pharmacology. Many anthelmintic drugs (e.g. suramin, diethylcarbamazine, hycanthone) were introduced before modern techniques for drug evaluation (controlled clinical trials) and before the development of specific and sensitive analytical methods for the assay of drugs and metabolites in biological fluids. Thus, many of the regimens used today for the treatment of parasitic diseases are largely empirically derived. By means of specific analytical methodology (high performance liquid chromatography, gas chromatography and mass-spectrometry) introduced in the 1960s, it is now possible to measure drugs and their metabolites with specificity and sensitivity. Much of this review deals with compounds which are active against the major systemic helminths, i.e., filariae (diethylcarbamazine, ivermectin and suramin) and schistosomes (niridazole, metrifonate, oxamniquine and praziquantel), but recent advances in the treatment of hydatid disease involving the benzimidazole carbamates albendazole and mebendazole are also discussed. Among the imidazole derivatives, mebendazole, a broad-spectrum anthelmintic, is poorly absorbed from the gastrointestinal tract after a therapeutic dose, but that fraction which is absorbed and escapes hepatic first-pass extraction is pharmacologically active against systemic helminths. Albendazole is more completely absorbed, but is almost undetectable in plasma due to its rapid conversion to an active sulphoxide metabolite. This compound may well become the drug of choice for the chemotherapy of echinococcosis. Levamisole, the 1-isomer of tetramisole, is rapidly and completely absorbed, but has not been widely used in systemic helminthiases because of severe side effects associated with prolonged dosage. Diethylcarbamazine is microfilaricidal against Onchocerca volvulus, but its use has been associated with major adverse effects resulting from its action on the microfilariae. These effects are related to the concentration of the drug in the plasma which, in turn, is influenced by urinary pH. The elimination half-life of diethylcarbamazine is prolonged and renal clearance reduced in alkaline urine. Under these conditions the microfilaricidal effect is enhanced, but the adverse reactions to treatment are more severe. Suramin is the only available antifilarial agent with macrofilaricidal activity. It has a long elimination half-life (36 to 54 days), and is highly (99.7%) bound to plasma protein which limits its removal from the blood.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Clinical Considerationsmentioning

confidence: 95%