THE USE OF SINGLE SAMPLE CLEARANCE ESTIMATES TO PROBE HEPATIC DRUG-METABOLISM - HANDPRINTING THE INFLUENCE OF PHENOBARBITONE ON HUMAN HEPATIC DRUG-METABOLISM

被引:8
作者
BACHMANN, KA [1 ]
NUNLEE, M [1 ]
MARTIN, M [1 ]
JAREGUI, L [1 ]
机构
[1] ST VINCENTS MED CTR,TOLEDO,OH 43606
关键词
D O I
10.3109/00498259109043213
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Single sample clearance estimates, CL, were calculated for seven drugs employed as probes of human hepatic drug-metabolizing enzymes. Clearance estimates were calculated in healthy young adult male volunteers either taking no pretreatment, or taking phenobarbitone (PB) 100 mg nightly for 3 nights. This intermittent regimen (3 nights on, followed by 4 nights off) was repeated for at least 3 consecutive weeks prior to challenge with an individual probe. 2. Valproic acid was selected as a probe of both peroxisomal and microsomal beta-oxidase activity; antipyrine, phenytoin, quinidine, and carbamazepine were selected as probes of hepatic mixed-function oxidases (MFO), and lorazepam as a probe for UDP-glucuronosyl transferase activity. 3. Clearances of all probes except lorazepam, theophylline and phenytoin were approximately 20-30% faster in PB-treated than in control subjects; however, only in the case of carbamazepine did the increased clearance approach statistical significance. Neither phenytoin nor theophylline clearances were increased by PB. 4. A clearance index (probe CL for PB-treated subjects divided by probe CL for untreated subjects) was calculated for each probe, and an ordinal transformation of the log of the resultant ratio was plotted for each probe giving rise to a 'handprint' of the effect of PB on drug-metabolizing activity.
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页码:1385 / 1392
页数:8
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