1 Four cytochrome P-450 enzyme activities, 7-ethoxyresorufin O-deethylase (ERDE), coumarin 7-hydroxylase (CH), 7-ethoxycoumarin 0-deethylase (ECDE) and aryl hydrocarbon hydroxylase (AHH) were measured in human liver needle biopsy samples from smokers and non-smokers. Cigarette smoking was verified and quantitated by measuring plasma cotinine levels.3 Enzyme inhibitory monoclonal antibodies (MAb) to a 3-methylcholanthrene-induced (MAb 1-7-1) and phenobarbitone-induced (MAb 2-66-3) rat hepatic cytochrome P-450 were used to measure the contribution of MAb-defined, epitope-specific cytochromes P-450 to the total reaction measured for each of the above activities. 3 ERDE activity was significantly elevated in the livers of cigarette smokers, whereas AHH, CH or ECDE activities were not affected by cigarette smoking. No correlation was observed between plasma cotinine concentration and ERDE activity. 4 MAb 1-7-1 inhibited hepatic ERDE activity to a variable extent (from 0 to 65%), but had very little or no effect on AHH, CH or ECDE activities. The inhibitory effect of MAb 1-7-1 on ERDE activity was greater than 50% in the non-smokers. MAb 2-66-3 had no inhibitory effect on any of the enzyme activities studied. 5 In contrast to liver both ERDE and AHH on human placental microsomes from cigarette smokers were inhibited by MAb 1-7-1. The MAb 2-66-3 was without effect. 6 Cigarette smoking induces a form of P-450 in human liver, responsible for ERDE activity, that contains an epitope recognized by MAb 1-7-1. This form of cytochrome P-450 is insensitive to MAb 2-66-3 and is not contributing to AHH, CH or ECDE activities of human liver.

No abstract

No abstract

1 The effects of hepatic microsomal enzyme inducing (phenobarbitone and flumecinol), and inhibiting (cimetidine) drugs, and placebo treatment on insulin mediated glucose metabolism (M) were investigated in 29 healthy volunteers. 2 Phenobarbitone (50 mg for 10 days) increased M (30%), metabolic clearance rate of glucose (MCRg), and antipyrine clearance rate (33%). Fasting immunoreactive insulin (IRI) decreased while fasting blood glucose (BG) remained unaltered. 3 Flumecinol, another inducer, tested in two doses (200 mg and 600 mg for 6 days), did not alter glucose or antipyrine metabolism. Fasting IRI reduced on treatment with 600 mg of flumecinol, but not with the smaller dose. 4 Cimetidine (600 mg for 6 days) decreased M (19.5%), MCRg (26%), and antipyrine clearance rate (20%). 5 The placebo did not alter glucose or antipyrine metabolism. 6 The results indicate that the insulin mediated glucose disposal rate can be altered by drugs influencing hepatic microsomal enzyme activity.

The distribution of acetylator phenotypes in a Hungarian population of 253 Caucasian was studied. The patients were divided into two age groups - the elderly over 60 years, and young below that age. The individuals below the age of 60 years contained an equal proportion of the two acetylator phenotypes. The same distribution was observed in the population as a whole. In the elderly subjects the slow acetylator phenotype was predominant. The finding supports the hypothesis that age has an influence on hepatic drug acetylation rate.