Quantitative and stereochemical aspects of glutethimide metabolism in humans.
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Adult↗
Biomedical subjects
L J Fischer
Publications and source records attributed to L J Fischer.
The excretion of tritium-labeled chlormadinone acetate, mestranol, norethindrone, and norethynodrel in rats and the enterohepatic circulation of metabolites.
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Analysis of Variance↗
Identification and activity of the hydroxy metabolite that accumulates in the plasma of humans intoxicated with glutethimide.
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Animals↗
Formation and urinary excretion of cyproheptadine glucuronide in monkeys, chimpanzees, and humans.
The urinary excretion of cyproheptadine glucuronide (a quaternary ammonium glucuronide) was studied in monkeys, chimpanzees, and humans after a single 5-mg oral dose of cyproheptadine. Humans and chimpanzees excreted, over a 48-hr period, an average 12.4 and 8.6% of the dose, respectively, as cyproheptadine glucuronide. Various species of monkeys excreted less than 0.5% of the dose as the quaternary ammonium glucuronide conjugate. According to these and previously published data, these unusual drug metabolites are excreted in the urine in relatively large amounts only in higher primates.
Adult↗
Phenytoin metabolism in mice.
The effect of dose on the metabolism of phenytoin (5,5-diphenylhydantoin, DPH) was investigated. A single ip injection of 14C-DPH (1, 20, or 100 mg/kg) was given to adult male mice, and urine and feces were collected over 72 hr. DPH and its metabolites excreted in urine were separated and analyzed by HPLC after beta-glucuronidase hydrolysis and extraction with ethyl acetate. The drug-related products measured in urine included: DPH, 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH), 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin, (DHD), 5-(3-methoxy-4-hydroxyphenyl)-5-phenylhydantoin (OMCAT), and diphenylhydantoic acid (DPHA). The percentage of the dose appearing as unchanged DPH and DPHA increased with dose, whereas that excreted as OMCAT decreased at higher doses. In contrast, the excretion of p-HPPH (approximately 30%) and DHD (approximately 12%) was independent of dose. The constant ratio of p-HPPH/DHD excreted in urine suggests that these metabolites have a common precursor, probably an arene oxide. Studies of the fate of DPH metabolites showed that a small fraction of a dose of p-HPPH or of DHD was converted to OMCAT. The catechol metabolite of DPH, therefore, arises via two different mechanisms.
Animals↗