Effect of Pentobarbital on the Formation of Diastereomeric Oxazepam Glucuronides in Man: Analysis by High Performance Liquid Chromatography
1981; Wiley; Volume: 49; Issue: 3 Linguagem: Inglês
10.1111/j.1600-0773.1981.tb00893.x
ISSN0001-6683
AutoresPeter Seideman, Örjan Ericsson, K Gröningsson, Christer von Bahr,
Tópico(s)Hormonal and reproductive studies
ResumoAbstract: Barbiturate treatment can enhance drug oxidation in man, but its effects on glucuronidation of clinically used drugs are unknown. We have studied the effect of 10 days treatment with pentobarbital on oxazepam glucuronidation in six volunteers. The diastereomeric (+ and minus;) glucuronides in urine were analyzed separately by high performance liquid chromatography and oxazepam in plasma by gas liquid chromatography. The area under the plasma concentration time curve for oxazepam (15 mg sod) decreased after pentobarbital treatment in all subjects, mean 10.4 before and 6.9 hXμmol/l after treatment (P<0.05) and oxazepam's plasma clearance increased by about 50 per cent. The glucuronides appeared more rapidly in the initial urinary fractions. The ratio between the glucuronides (+/minus;) appearing in urine decreased on pentobarbital treatment. Our data indicate that pentobarbital treatment increases the clearance of oxazepam by increased glucuronide conjugation, probably reflecting barbiturate induced changes of UDP glucuronyltransferase.
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