咪哒唑仑在两个年龄组的药物动力学

Comparation of pharmacokinetic characteristics of midazolam in two age groups

对健康男性较高年龄及青年志愿者各７例，分别单次快速静滴０．０８ｍｇ／ｋｇ及０．１２ｍｇ／ｋｇ咪哒唑仑后，进行了药物动力学研究。结果两组药物动力学均成二室模型。较高年龄组比青年组的室间转运速率常数Ｋ１２、末相半衰期Ｔ１／２β和平均滞留时间ＭＲＴ０－∞均明显增大，两组Ｋ１２分别为７±６ｈ和２．８±１．４ｈ（Ｐ＜０．０５），Ｔ１／２β为４．０±１．７ｈ和２．１±０．６ｈ（Ｐ＜０．０１），ＭＲＴ０－∞为５．２±１．８ｈ和２．５±０．７ｈ（Ｐ＜０．０１）；而总清除率ＣＬｓ较高年龄组比青年组明显减小，分别为０．１７±０．０３Ｌ／（ｋｇ·ｈ）和０．２８±０．０８Ｌ／（ｋｇ·ｈ）（Ｐ＜０．０１）。且中国人ＣＬｓ较欧洲人为低。提示年龄增大对咪哒唑仑的清除能力下降，中国男性老年人给药剂量和给药间隔应适当调整。

lasma concentration was determined with HPLC after short intravenous infusion of 0.08 mg/kg and 0.12 mg/kg midazolam in 7 elder males and 7 young males respectively.All the time concentration curves in the volunteers of the two groups were fit to two compartment model. The transport parameters between compartment ( K 12 ) was 7±6h -1 in elder males and 2.8 ± 1.4 h -1 in young males ( P < 0.05 ).Elimination half life ( T 1/2 ) and mean residence time ( MRT 0￣∞ were prolonged in elder males versus young males ( 2.1 ± 0.6 h vs 4.0 ± 1.7 h, 2.5 ± 0.7 h vs 5.2 ± 1.8 h, P < 0.01 ).The total clearence ( CLs ) in young males which was lower than europeans was significantly higher than elder males ( 0.28 ± 0.08 vs 0.17 ± 0.03 (L/kg)·h, P < 0.01 ).Our results suggest that the dosage of midazolam should be adjusted in aged Chinese males.