Lack of in vitro and in vitro effects of fenbendazole on phase I and phase II biotransformation enzymes in rats, mice and chickens.
Intraperitoneal administration of 10 mg fenbendazole/kg bw daily for 5 d caused no significant alterations in the activities of hepatic microsomal drug-metabolizing enzymes viz aminopyrine N-demethylase, aniline hydroxylase and cytosolic glutathione S-transferase in rats, mice and chickens. Similarly no significant difference in the amount of microsomal cytochrome P-450 and NADPH-cytochrome c reductase was found between control and treated animals. In vitro incubation of fenbendazole with rat, mouse and chicken microsomes suggests that the drug neither binds to microsomal protein cytochrome P-450 nor inhibits the activities of aminopyrine N-demethylase and aniline hydroxylase. Similarly in vitro addition of fenbendazole to cytosolic glutathione S-transferase from the above species did not alter the activity of this enzyme. The results indicate that fenbendazole does not alter the activity of hepatic microsomal monooxygenase system significantly in rats, mice and chickens at a dosage level of 10 mg/kg body weight. In vitro studies also indicate that fenbendazole does not interact with the hepatic microsomal monooxygenase system, indicating it is not a substrate for cytochrome P-450-dependent monooxygenase system.
Dalvi
R R
RR
Department of Physiology and Pharmacology, School of Veterinary Medicine, Tuskegee University, AL 36088.
Gawai
K R
KR
Dalvi
P S
PS
D000633:Aminopyrine N-Demethylase / Q000187:drug effects / Q000378:metabolism; D000815:Aniline Hydroxylase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002645:Chickens; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D005273:Fenbendazole / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D005273:Fenbendazole; D003577:Cytochrome P-450 Enzyme System; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase