Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.
Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.
复制标题
哺乳期妇女的药代动力学：阿普唑仑转移到乳汁中的预测。
DOI：
10.1111/j.1365-2125.1995.tb05778.x
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发表时间：
1995
影响因子：
3.4
通讯作者：
McNamara,PJ
中科院分区：
文献类型：
--
作者：
Oo,CY;Kuhn,RJ;Desai,N;Wright,CE;McNamara,PJ
1.阿普唑仑是一种三唑苯并二氮卓类药物，广泛用于治疗焦虑症，主要影响育龄妇女。本研究的目的是评估阿普唑仑及其两种羟基化代谢产物（4-羟基-阿普唑仑和α-羟基-阿普唑仑）在哺乳期人类志愿者中的药代动力学，并基于理化性质检测最近报告的4种药物转移至乳汁模型的可预测性。2.在8名哺乳期受试者中采集了多份乳汁和血清样本，采集时间为0.5 mg阿普唑仑单次口服给药后36 h;给药后婴儿停止哺乳。4-羟基-阿普唑仑是血清样本中的主要代谢产物，而未检出α-羟基-阿普唑仑。3.阿普唑仑的平均口服清除率为1.15 +/-0.32 ml min-1 kg-1。乳汁中阿普唑仑的时间过程大致符合预期血浆时间曲线（平均血清停留时间= 16.42 +/-4.69 h;平均乳汁停留时间= 18.93 +/-7.03 h）。血清中的平均终末半衰期为12.52 +/-3.53 h。4.在体内测定观察到的乳汁/血清浓度比，表示为AUC乳汁/AUC血清（平均M/S（obs）= 0.36 +/-0.11）。（250字处删节）
1. Alprazolam, a triazolobenzodiazepine, is extensively prescribed for the treatment of anxiety disorders, which predominantly affect women of child‐bearing age. The purpose of the present study was to assess the pharmacokinetics of alprazolam and its two hydroxylated metabolites: 4‐ hydroxy‐alprazolam and alpha‐hydroxy‐alprazolam in lactating human volunteers and to test the predictability of four recently reported models for drug transfer into milk based on physicochemical properties. 2. Multiple milk and serum samples in eight lactating subjects were collected up to 36 h following single oral doses of 0.5 mg alprazolam; suckling of the infant was discontinued after drug administration. 4‐ Hydroxy‐alprazolam was the predominant metabolite in serum samples while alpha‐hydroxy‐alprazolam was not detected. 3. The mean oral clearance of alprazolam was 1.15 +/‐ 0.32 ml min‐1 kg‐1. The time course of alprazolam in milk roughly paralleled the perspective plasma time profile (mean serum residence time = 16.42 +/‐ 4.69 h; mean milk residence time = 18.93 +/‐ 7.03 h). The mean terminal half‐life in serum was 12.52 +/‐ 3.53 h. 4. Observed milk/serum concentration ratios were determined in vivo as AUCmilk/AUCserum (mean M/S(obs) = 0.36 +/‐ 0.11).(ABSTRACT TRUNCATED AT 250 WORDS)