美西律在人体中的立体选择性分布。
Stereoselective disposition of mexiletine in man.
作者信息
Grech-Belanger O, Turgeon J, Gilbert M
出版信息
Br J Clin Pharmacol. 1986 May;21(5):481-7. doi: 10.1111/j.1365-2125.1986.tb02829.x.
Abstract
The pharmacokinetics of S-(+)- and R-(-)-mexiletine and of the corresponding conjugates were investigated in six healthy young volunteers after administration of a single 200 mg oral dose of racemic mexiletine hydrochloride. The values for the distribution rate constants as well as for the elimination half-lives of the two enantiomers were similar but the AUC of the S-(+)-enantiomer was always significantly higher (P less than 0.01) than that of the opposite enantiomer. The mean R/S ratios for unchanged mexiletine in serum and in urine were 0.78 +/- 0.12 (s.d.) and 0.80 +/- 0.21, respectively. Urinary excretion of mexiletine conjugates consisted mainly of the R-(-)-enantiomer; the mean R/S enantiomeric ratio over 48 h was 9.65 +/- 3.10. Serum concentrations of the conjugates were measured in three subjects. The mean R/S AUC ratio was 2.94 +/- 0.48 and the renal clearance of the R-(-)-enantiomer was significantly higher (P less than 0.02) than that of the S-(+)-enantiomer.
摘要
在6名健康年轻志愿者单次口服200mg消旋盐酸美西律后，对S-(+)-和R-(-)-美西律及其相应结合物的药代动力学进行了研究。两种对映体的分布速率常数和消除半衰期值相似，但S-(+)-对映体的AUC总是显著高于（P<0.01）其对映体。血清和尿液中未变化美西律的平均R/S比值分别为0.78±0.12（标准差）和0.80±0.21。美西律结合物的尿排泄主要由R-(-)-对映体组成；48小时内的平均R/S对映体比值为9.65±3.10。在三名受试者中测量了结合物的血清浓度。平均R/S AUC比值为2.94±0.48，R-(-)-对映体的肾清除率显著高于（P<0.02）S-(+)-对映体。
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