Abstract
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 t 1 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 microsamal fractions obtained from the livers. Cytochrome P-450 catalyzed p-nitroanisole-demethylase a activity in the microsamal fractions in vitro was inhibited in the first 24 h and induced in microsomes prepared after that time.
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