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 biochemical parameters have been followed to monitor the efficacy of the treatments. While Fascinex (triclabendazole) efficiently cured both male and female rats when administered as soon as 4 weeks postinfection, treatment with Ivomec-D (clorsulon + ivermectin) displayed a low efficacy on either male or female rats at this time point (54 and 0%, respectively). Moreover, when administered 8 weeks postinfection, the Ivomec-D treatment proved highly efficient on male rats while it displayed little effect on the female population (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 on drug metabolism and the need for the incorporation of both genders in clinical trials are discussed.
Sibille
P
P
Station de Pathologie Aviaire et Parasitologie, INRA, Nouzilly, 37380, France.
Calléja
C
C
Carreras
F
F
Bigot
K
K
Galtier
P
P
Boulard
C
C
D000818:Animals; D000871:Anthelmintics / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000909:Antibodies, Helminth / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000097:blood; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005210:Fasciola hepatica / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification; D005211:Fascioliasis / Q000188:drug therapy* / Q000378:metabolism; D005243:Feces / Q000469:parasitology; D005260:Female; D007559:Ivermectin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000469:parasitology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013424:Sulfanilamides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000077682:Triclabendazole
D000871:Anthelmintics; D000909:Antibodies, Helminth; D001562:Benzimidazoles; D004338:Drug Combinations; D013424:Sulfanilamides; D000077682:Triclabendazole; D007559:Ivermectin; D003577:Cytochrome P-450 Enzyme System; D001219:Aspartate Aminotransferases; C015675:clorsulon