Hepatic clotrimazole concentrations and hepatic drug metabolizing enzyme activities in adult male Sprague-Dawley rats.
A single high dose, 75 mg/kg, of clotrimazole (CloTZ) was administered intragastrically (i.g.) to adult male Sprague-Dawley rats. Hepatic CloTZ concentrations were determined in organic extracts of whole liver homogenate, by high-performance liquid chromatography (HPLC). The peak liver CloTZ concentration was found at 2.5 h post dose, and the liver t1/2 was 11 h. With the present procedure CloTZ was detectable in the liver for up to 40 h and during this period, the hexobarbital sleep-time in these treated rats was prolonged. Between 40 and 120 h following a single dose of CloTZ, hexobarbital sleep-times were less than in untreated rats. The shortened sleep-time coincided with cytochrome P-450 induction which could be demonstrated in microsomal fractions obtained from the livers. Cytochrome P-450 catalyzed p-nitroanisole-demethylase activity in the microsomal fractions in vitro was inhibited in the first 24 h and induced in microsomes prepared after that time.
Pappas
J B
JB
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Franklin
M R
MR
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003022:Clotrimazole / Q000378:metabolism / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006591:Hexobarbital / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects
D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D003022:Clotrimazole