Fasciola hepatica: Influence of gender and liver biotransformations on flukicide treatment efficacy of rats infested and cured with either clorsulon/ivermectin or triclabendazole

Two fasciolicide preparations have been compared in 130 rats experimentally infected with Fasciola hepatica. Parasitological, immunological, and bioch emical parameters have been followed to monitor the efficacy of the treatme nts. While Fascinex (triclabendazole) efficiently cured both male and femal e rats when administered as soon as 4 weeks postinfection, treatment with I vomec-D (clorsulon + ivermectin) displayed a low efficacy on either male or female rats at this time point (54 and 0%, respectively). Moreover, when a dministered 8 weeks postinfection, the Ivomec-D treatment proved highly eff icient on male rats while it displayed little effect on the female populati on (100 and 53%, respectively). This unexpected result has been related to an overexpression of a P4503A isoform that is observed only in females that have been treated with Ivomec-D. The influence of this P4503A cytochrome o n drug metabolism and the need for the incorporation of both genders in cli nical trials are discussed. (C) 2000 Academic Press.