在中国受试者中，地西泮的消除取决于美芬妥因氧化表型。

The elimination of diazepam in Chinese subjects is dependent on the mephenytoin oxidation phenotype.

Wan J, Xia H, He N, Lu Y Q, Zhou H H

Pharmacogenetics Research Institute, Human Medical University, Changsha, China.

Br J Clin Pharmacol. 1996 Oct;42(4):471-4. doi: 10.1046/j.1365-2125.1996.42712.x.

Abstract

The disposition of diazepam and desmethyldiazepam was studied in 21 healthy male Chinese subjects who were phenotyped with mephenytoin. Four poor metabolizers (PM) were identified by phenotyping with mephenytoin and by genotyping for CYP2C19. 2. Serum diazepam and desmethyldiazepam concentrations were measured by high performance liquid chromatography in samples drawn up to 24 days after administration. 3. The plasma elimination half-lives of diazepam (100.8 +/- 32.3 h) and desmethyldiazepam (219.9 +/- 62.7 h) in PMs were significantly longer than those (34.7 +/- 23.0 h for diazepam, 103.1 +/- 25.9 h for desmethyldiazepam) of the 17 phenotyped extensive metabolizers (EM), and those (30.8 +/- 24.9 h for diazepam, 103.1 +/- 27.5 h for desmethyldiazepam) of the five genotyped EMs. 4. The mephenytoin S/R ratios were significantly correlated with the plasma half-lives of diazepam (r = 0.543, P < 0.05) and desmethyldiazepam (r = 0.522, P < 0.05), and with the clearance (r = -0.524, P < 0.05) of diazepam in 21 subjects. 5. These results are compatible with the conclusion that both diazepam and desmethyldiazepam are metabolized by cytochrome P450 CYP2C19 in the Chinese population. 6. The mephenytoin S/R ratios in nine EMs who drank alcohol frequently were significantly higher than those of seven EMs who were non-drinkers, but the plasma kinetics of diazepam and desmethyldiazepam were not significantly different between the two groups. The explanation for these finding is not clear.

摘要

在21名健康中国男性受试者中研究了地西泮和去甲地西泮的处置情况，这些受试者用美芬妥因进行了表型分析。通过美芬妥因表型分析和CYP2C19基因分型鉴定出4名慢代谢者（PM）。2. 在给药后长达24天采集的样本中，通过高效液相色谱法测定血清地西泮和去甲地西泮浓度。3. 慢代谢者中地西泮（100.8±32.3小时）和去甲地西泮（219.9±62.7小时）的血浆消除半衰期显著长于17名表型分析为快代谢者（EM）的相应半衰期（地西泮为34.7±23.0小时，去甲地西泮为103.1±25.9小时），也长于5名基因分型为快代谢者的相应半衰期（地西泮为30.8±24.9小时，去甲地西泮为103.1±27.5小时）。4. 在21名受试者中，美芬妥因S/R比值与地西泮的血浆半衰期（r = 0.543，P < 0.05）和去甲地西泮的血浆半衰期（r = 0.522，P < 0.05）以及地西泮的清除率（r = -0.524，P < 0.05）显著相关。5. 这些结果与以下结论一致：在中国人群中，地西泮和去甲地西泮均由细胞色素P450 CYP2C19代谢。6. 9名经常饮酒的快代谢者的美芬妥因S/R比值显著高于7名不饮酒的快代谢者，但两组之间地西泮和去甲地西泮的血浆动力学无显著差异。这些发现的解释尚不清楚。