Kristensen K, Blemmer T, Angelo H R, Christrup L L, Drenck N E, Rasmussen S N, Sjøgren P
Department of Pharmaceutics, Royal Danish School of Pharmacy, Copenhagen, Denmark.
Ther Drug Monit. 1996 Jun;18(3):221-7. doi: 10.1097/00007691-199606000-00001.
Ten patients with chronic pain were randomized to an open, balanced, crossover study. Each patients received two different preparations of racemic methadone, i.e., tablets and intravenous infusion. The pharmacokinetic parameters of the R- and S-enantiomers of the racemate are reported. The analgesically active R-methadone has a significantly longer mean elimination half-life than the optical antipode S-methadone (t1/2 = 37.5 and 28.6 h, respectively). The mean total volume of distribution is 496.6 L for R-methadone and 289.1 L for S-methadone. Significant differences in the mean clearance between R- and S-methadone are seen (0.158 and 0.129 L/min, respectively). However, the lagtime after oral administration and the bioavailability did not show differences between the isomers. The data suggest that both enantiomers of methadone should be measured if correlations between pharmacodynamics and kinetics are made due to the stereoselective differences in half-life, total volume of distribution, and clearance.
十名慢性疼痛患者被随机分配到一项开放性、均衡、交叉研究中。每位患者接受两种不同的消旋美沙酮制剂，即片剂和静脉输注。报告了消旋体的R-和S-对映体的药代动力学参数。具有镇痛活性的R-美沙酮的平均消除半衰期明显长于其旋光对映体S-美沙酮（分别为t1/2 = 37.5小时和28.6小时）。R-美沙酮的平均总体分布容积为496.6升，S-美沙酮为289.1升。R-和S-美沙酮之间的平均清除率存在显著差异（分别为0.158和0.129升/分钟）。然而，口服给药后的滞后时间和生物利用度在异构体之间没有差异。数据表明，如果由于半衰期、总体分布容积和清除率的立体选择性差异而进行药效学和动力学之间的相关性研究，则应测量美沙酮的两种对映体。
