Pharmacokinetics and pharmacodynamics of triazolam after two intermittent doses in obese and normal-weight men.
Pharmacokinetics and pharmacodynamics of triazolam after two intermittent doses in obese and normal-weight men.
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肥胖和正常体重男性间歇服用两次三唑仑后的药代动力学和药效学。
DOI：
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发表时间：
1995
影响因子：
2.9
通讯作者：
R. Smith
中科院分区：
文献类型：
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作者：
C. Derry;P. Kroboth;A. Pittenger;F. Kroboth;S. E. Corey;R. Smith
本研究旨在确定α -1酸性糖蛋白和游离药物浓度的差异是否会导致对三唑仑的反应改变。12名体重正常的成年男性和12名肥胖的成年男性受试者接受静脉注射剂量为0.5 mg的三唑仑，两次静脉注射，间隔1周。各组间α -1酸性糖蛋白浓度差异不大，但三唑安定游离部分无差异。肥胖组终末半衰期（t1/2 β）较长（3.16 +/- 0.87比3.83 +/- 1.24,p = 0.0098）。总体而言，第1周的数据显示正常和肥胖受试者之间的效果没有差异。然而，反应数据显示，第二次暴露于三唑仑增加敏感性的模式。例如，两组受试者在第2周的所有测试中，效果曲线下面积（AUEC）都显著增加。在0 ~ 12小时的记忆测试和镇静中，所有受试者的AUC /自由AUC比率在第2周显著增加。第2周的肥胖比例高于第1周，所有精神运动测试和镇静（0 ~ 4.5 h; p < 0.05）。各组每周汇总的精神运动障碍集中数据的建模结果延续了这种模式：第1周的数据在肥胖和正常体重的受试者之间相似。虽然正常体重受试者的EC50值在第二周降低了15%，但肥胖受试者的EC50值在第二周降低了66%，其中较低的EC50表示更敏感。对识别数据进行逻辑回归分析，结果与上述结果一致。（摘要删节250字）
This study was designed to determine whether differences in alpha-1 acid glycoprotein and free drug concentrations result in an altered response to triazolam. Twelve normal-weight and 12 obese adult male subjects received intravenous doses of triazolam, 0.5 mg, on two occasions separated by 1 week. There was a small difference in the alpha-1 acid glycoprotein concentrations between groups but no difference in free fraction of triazolam. There was a longer terminal half-life (t1/2 beta) in the obese subjects (3.16 +/- 0.87 vs. 3.83 +/- 1.24, p = 0.0098). Overall, week 1 data revealed no difference in effect between normal and obese subjects. However, response data reveal a pattern of increased sensitivity with the second exposure to triazolam. For example, area under the effect curve (AUEC) on all tests was significantly greater in week 2 for both groups of subjects. For a memory test and sedation from 0 to 12 hours, AUEC/free AUC ratios were significantly greater in week 2 for all subjects. The obese had a higher ratio on week 2 than on week 1 for all psychomotor tests and sedation (0 to 4.5 hours; p < 0.05). The results of modeling psychomotor impairment-concentration data pooled by group for each week continue the pattern: week 1 data are similar between the obese and normal-weight subjects. Although EC50 values are up to 15% lower in week 2 for the normal-weight subjects, EC50 values are as much as 66% lower in week 2 for the obese, where a lower EC50 indicates greater sensitivity. Logistic regression of the recognition data is consistent with these results.(ABSTRACT TRUNCATED AT 250 WORDS)
DOI：
10.1038/npp.1993.30
发表时间：
1993
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
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作者：
Byrnes,JJ;Miller,LG;Perkins,K;Greenblatt,DJ;Shader,RI
通讯作者：
Shader,RI
三唑并苯二氮卓类药物阿普唑仑和三唑仑的电子捕获气相色谱分析。
DOI：
10.1016/s0378-4347(00)80261-3
发表时间：
1981
期刊：
Journal of chromatography
影响因子：
--
作者：
Greenblatt,DJ;Divoll,M;Moschitto,LJ;Shader,RI
通讯作者：
Shader,RI