The chemotherapy of onchocerciasis XVII. A clinical evaluation of albendazole in patients with onchocerciasis; effects of food and pretreatment with ivermectin on drug response and pharmacokinetics.

Three pharmacokinetic studies were conducted in Ghanaian patients in support of investigations of albendazole and its combination with ivermectin in the treatment of onchocerciasis. These included dose-finding studies, investigations into the influence of a fatty meal on the relative bioavailability of albendazole as assessed by the measurement of concentrations of albendazole sulphoxide and the effect of prior treatment with ivermectin on antiparasitic efficacy and plasma concentrations of albendazole suphoxide. Increasing the dose of albendazole from 800 mg x 3 daily to 1200 mg x 3 daily produced no additional antiparasitic effects although plasma concentrations of albendazole sulphoxide were increased in proportion to dose size. Moreover, the plasma concentration vs time profiles suggest that most of the effects observed may have been due to the first 800 mg dose. Administration of ivermectin had no effect on the pharmacokinetics of albendazole sulphoxide and there was no additive effect on the parasite. Albendazole was well tolerated and its administration 5-7 days after ivermectin produced little additional reaction. Although it is not macrofilaricidal, it does possess important chemosterilant properties which are enhanced by its administration with a fatty breakfast. Under these conditions, the relative bioavailability of albendazole is increased four-fold. These studies support further work with albendazole administered with food either as a single dose, as multiple single doses repeated at intervals of several months and its coadministration with ivermectin. They also encourage the belief that a more potent and bioavailable benzimidazole may be macrofilaricidal or a permanent chemosterilant for Onchocerca volvulus on single dosage.

RCT Entities:   Population Interventions Outcomes