Comparison of the plasma and urinary metabolites of [3H]-econazole nitrate in the monkey and pregnant and non-pregnant rat

Autor: R. R. Brodie, I Midgley, L. F. Chasseaud, R. Girkin, D. R. Hawkins
Rok vydání: 1983
Předmět:
Zdroj: European Journal of Drug Metabolism and Pharmacokinetics. 8:109-116
ISSN: 2107-0180
0378-7966
DOI: 10.1007/bf03188736
Popis: Concentrations of total radioactivity, unchanged econazole, and extractable metabolites in plasma, and chromatographic patterns of radioactive components in urine, have been determined after single oral doses of [3H]-econazole nitrate to nonpregnant rats and monkeys (10 mg/kg) and pregnant rats (10 and 50 mg/kg). Plasma3H-concentration-time profiles were qualitatively similar for all groups of rats in that each exhibited two distinct maxima, whereas the corresponding monkey profiles only exhibited a single maximum. Concentrations declined relatively slowly and radioactivity was still detectable at 48 hours (rats) or 120 hours (monkeys). Little or no unchanged econazole was present in the plasma of either species after the lower dose, but notable concentrations were found in pregnant rats receiving the higher dose. Most of the extractable radioactivity in plasma was associated with three metabolites which had suffered oxidative biotransformation in the imidazole ring. Concentrations of these metabolites were generally lower in monkey plasma than in rat plasma. Renal excretion appeared to be a more important route of elimination of the dose for the monkey than for the rat, and although no unchanged econazole was excreted in this way by either species, their patterns of urinary metabolites exhibited several important differences. Thus, monkey urine contained a greater proportion of the glucuronide (or sulphate) conjugates of metabolites which had lost thep-chlorobenzyl group as well as having suffered oxidation of the heterocyclic ring, whereas rat urine contained more of a less polar metabolite tentatively identified as econazole-N-oxide.
Databáze: OpenAIRE
Externí odkaz: