INCREASE OF CYTOCHROME-P450IA2 ACTIVITY BY OMEPRAZOLE - EVIDENCE BY THE C-13-[N-3-METHYL]-CAFFEINE BREATH TEST IN POOR AND EXTENSIVE METABOLIZERS OF S-MEPHENYTOIN

被引:132
作者
ROST, KL
BROSICKE, H
BROCKMOLLER, J
SCHEFFLER, M
HELGE, H
ROOTS, I
机构
[1] FREE UNIV BERLIN,KLINIKUM STEGLITZ,INST KLIN PHARMAKOL,HINDENBURGDAMM 30,W-1000 BERLIN 45,GERMANY
[2] FREE UNIV BERLIN,KLINIKUM RUDOLF VIRCHOW,DEPT PAEDIAT,W-1000 BERLIN 33,GERMANY
关键词
D O I
10.1038/clpt.1992.126
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Omeprazole has been shown to induce cytochrome P450IA1 and P450IA2 activity in vitro. To reflect cytochrome P45OIA2 (CYP1A2) activity in vivo, the C-13-[N-3-methyl]-caffeine breath test was conducted in 18 volunteers: 12 extensive metabolizers, one intermediate metabolizer, and five poor metabolizers of S-mephenytoin. Breath tests wert performed before treatment with an oral dose of 40 mg omeprazole, on the seventh day of treatment, and after a 7-day washout period. The mean percentage exhalation of the C-13 test dose, as determined by (CO2)-C-13 in breath during 8 hours, was 23.0% +/- 8.0% (n = 18) before treatment. The largest increases in exhalation rate of (CO2)-C-13 were observed in the poor metabolizers and the intermediate metabolizers (range, 12.8% to 62.9%; median, 38.9%); median area under the plasma concentration-time curves (AUC) of omeprazole was four times higher than in the extensive metabolizers. The change after omeprazole treatment in extensive metabolizers ranged from -9.8% to +47.7% (median, 12.3%; n = 12) of pretreatment values. In both groups exhalation rates of (CO2)-C-13 returned to near pretreatment values within the 7-day washout period (24.2% +/- 7.8%; n = 17). Changes in the C-13-caffeine breath test correlated well with both the pretreatment value (R = -0.67, p = 0.003; n = 18) and the plasma AUC of omeprazole (R = 0.61, p = 0.007; n = 18). Therapeutic doses of omeprazole seem to induce CYP1A2 activity in poor metabolizers, whereas they exert minor inducing effects in extensive metabolizers of S-mephenytoin.
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页码:170 / 180
页数:11
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