Clinical Pharmacokinetics of Anthelmintic Drugs

Abstract

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)

In vitro anthelmintic effect of Tobacco (Nicotiana tabacum) extract on parasitic nematode, Marshallagia marshalli

“…All the worms exposed to levamisole, a standard anthelmintic agent (Edwards and Breckenridge 1988), were found dead at 8 h; whereas, none of the worms were found dead or paralysed in PBS which acted as the negative control.…”

Improved Albendazole Dissolution Rate in Pluronic 188 Solid Dispersions

“…Several studies suggest that only limited absorption of BZD anthelmintics are achieved in cats, dogs and humans, owed mainly to their low dissolution rate on the gastric fluid. Consequently, these compounds have to be administrated at higher doses or as multiple doses in order to provide therapeutic concentrations and acceptable anthelmintic efficacy (22,23,24). Because of this particular behavior of BZD, the development of optimized pharmaceutical formulations remained as a challenging task.…”

Adverse Events from a Randomized, Multi-Arm, Placebo-Controlled Trial of Mebendazole in Children 12–24 Months of Age

“…All serious adverse events occurred at least 6 days (range = 6-227 days) after mebendazole administration, well after the complete clearance of the drug, which occurs in less than 24 hours. 16 The majority of serious adverse events (72.2%) were reported before the 18-month visit. There was a range of diagnoses reported, none of which were deemed to be related to anthelminthic use before unblinding (i.e., based on the symptoms or the timing at which the event occurred) by the research team, ethics committees, or the DSMC.…”