Effect of Pentobarbital on the Formation of Diastereomeric Oxazepam Glucuronides in Man: Analysis by High Performance Liquid Chromatography

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Abstract
Barbiturate treatment can enhance drug oxidation in man, but its effects on glucuronidation of clinically used drugs are unknown. The effect of 10 days treatment with pentobarbital were studied on oxazepam glucuronidation in 6 volunteers. The diastereomeric (+ and -) glucuronides in urine were analyzed separately by high performance liquid chromatography and oxazepam in plasma by GLC. The area under the plasma concentration time curve for oxazepam (15 mg single oral dose) decreased after pentobarbital treatment in all subjects, mean 10.4 before and 6.9 h .times. .mu.mol/l after treatment (P < 0.05), and oxazepam''s plasma clearance increased by .apprx. 50%. The glucuronides appeared more rapidly in the initial urinary fractions. The ratio between the glucuronides (+/-) appearing in urine decreased on pentobarbital treatment. Pentobarbital treatment increases the clearance of oxazepam by increased glucuronide conjugation, probably reflecting barbiturate induced changes of UDP glucuronyltransferase.