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.
D000328:Adult; D000368:Aged; D000983:Antipyrine / Q000097:blood; D001463:Barbiturates / Q000378:metabolism*; D004361:Drug Tolerance; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008702:Methaqualone / Q000378:metabolism*; D008875:Middle Aged; D011239:Prednisolone / Q000652:urine; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000378:metabolism*
D001463:Barbiturates; D008702:Methaqualone; D011239:Prednisolone; D000983:Antipyrine