Impairment of diazepam metabolism by low-dose estrogen-containing oral-contraceptive steroids.
Impairment of diazepam metabolism by low-dose estrogen-containing oral-contraceptive steroids.
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低剂量含雌激素的口服避孕药类固醇会损害地西泮代谢。
DOI：
10.1056/nejm198204013061307
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发表时间：
1982
期刊：
影响因子：
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通讯作者：
Shader,RI
中科院分区：
文献类型：
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作者：
Abernethy,DR;Greenblatt,DJ;Divoll,M;Arendt,R;Ochs,HR;Shader,RI
PIP：报告了长期使用低剂量含雌激素的口服避孕药（OC）及其对地西泮清除率的损害。8名年龄在52至72岁之间的健康女性参与了这项研究。所有的妇女都服用了3个月以上的低剂量含雌激素的OC。其中1例受试者吸烟。8名不使用OC的健康对照（均为非吸烟者）也参与了研究。他们的年龄从27岁到31岁不等。在15-30秒内通过静脉输注给予地西泮（10 mg）。在输注前、输注结束时、输注后5、15、30和45分钟、1、1.5、2、2.5、3、4、6、8、12和24小时以及7天内每天抽取静脉血样至肝素化试管中。采用加权迭代非线性最小二乘回归技术分析静脉输注后地西泮的血药浓度。两组间地西泮的分布容积无显著差异，但OC使用者地西泮的表观消除半衰期显著长于对照组，总代谢清除率显著低于对照组。这些差异未受到蛋白结合变化的混淆。2组的平均地西泮游离分数相同。本文报告的地西泮清除率降低的临床结果是以给定日剂量长期使用后地西泮稳态血浆浓度升高，可能增加地西泮在该人群中的临床效应。
PIP: The longterm use of low-dose estrogen containing oral contraceptives (OCs) and its impairment of diazepam clearance is reported. 8 healthy women, ranging in age from 52 to 72 years, participated in the study. All of the women had been taking low-dose estrogen containing OCs for more than 3 months. 1 of the subjects was a cigarette smoker. 8 healthy controls (all nonsmokers) who were not using OCs also participated. They ranged in age from 27-31 years. Diazepam (10 mg) was given by intravenous infusion over 15-30 seconds. Venous blood samples were drawn into heparinized tubes before the infusion, at the end of the infusion, at 5, 15, 30, and 45 minutes, at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours, and daily for 7 days after the infusion. Plasma concentrations of diazepam after intravenous infusion were analyzed by weighted iterative nonlinear least-squares regression techniques. The volume of distribution of diazepam was not significantly different between the groups, but the apparent elimination half-life of diazepam was significantly longer and the total metabolic clearance significantly less in the OC users than in the control group. The differences were not confounded by variations in protein binding. The mean diazepam free fraction was identical in the 2 groups. The clinical result of the decrease in diazepam clearance reported here would be increased steady-state plasma diazepam concentration after longterm use at a given daily dose, with the potential for increasing the clinical effects of diazepam in this population.