Drug-metabolizing capacity in states of drug dependence and withdrawal

1. Drug-metabolizing capacity was assessed in 8 barbiturate-dependent and in 3 Mandrax-dependent patients using, as indices, plasma antipyrine half-life and in some cases urinary output of 6beta-hydroxycortisol. For comparison, antipyrine half-life was also measured in volunteers before and after a period of taking hypnotic doses of these agents.2. Both indices indicated a very high drug-metabolizing capacity in the dependent subjects on admission, the antipyrine half-life value in the barbiturate patients being the shortest reported to date for any drug-exposed group. The urinary output of 6beta-hydroxycortisol was approximately three times that in a control population.3. This induction of drug-metabolizing capacity presumably contributed to the marked drug tolerance observed in the dependent patients.4. It appeared that drug-metabolizing capacity eventually returned to normal levels after withdrawal of the barbiturate.5. It is concluded that the abnormal drug-metabolizing capacity of dependent patients must be taken into account in assessing dose requirements for other drugs.