COMPARATIVE PHARMACOLOGY OF THE KETAMINE ISOMERS - STUDIES IN VOLUNTEERS
COMPARATIVE PHARMACOLOGY OF THE KETAMINE ISOMERS - STUDIES IN VOLUNTEERS
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DOI：
10.1093/bja/57.2.197
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发表时间：
1985-01-01
影响因子：
9.8
通讯作者：
TREVOR, AJ
中科院分区：
文献类型：
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作者：
WHITE, PF;SCHUTTLER, J;TREVOR, AJ
在5名志愿者中，比较了单独的氯胺酮异构体和外消旋混合物的临床和脑电效果，这些志愿者在不同的场合分别服用了这两种药物。外消旋氯胺酮275。+-。25 mg，S(+)氯胺酮140。+-。21毫克或R(-)氯胺酮429+-。37毫克产生持续6+-的麻醉状态。2分钟(平均+-SD)。对R(-)异构体的脑电分析表明，R(-)异构体的整体减慢较小，并且没有S(+)异构体和外消旋混合物产生的大的慢波复合波。氯胺酮的各个异构体的药代动力学曲线与外消旋混合物没有显著差异。尽管这些健康志愿者产生的表观麻醉状态在3个药物组之间没有本质上的差异，但恢复时间(使用标准化的一组心理测量测试进行评估)始终比使用外消旋混合物的个体异构体更短。与清醒和定向相关的氯胺酮血药浓度符合S(+)：R(-)异构体效价比4：1。就其损害精神运动功能的能力而言，S(+)：R(-)效价比在3：1-5：1之间变化。在同等程度的中枢神经系统抑郁后，与目前使用的外消旋混合物相比，更强的S(+)氯胺酮异构体与精神运动技能的恢复更快相关。
The clinical and EEG effect of the individual ketamine isomers were compared with the racemic mixture in 5 volunteers who received each drug on a separate occasion. Racemic ketamine 275 .+-. 25 mg, S(+) ketamine 140 .+-. 21 mg or R(-) ketamine 429 .+-. 37 mg produced an anesthetic state lasting 6 .+-. 2 min (mean .+-. SD). The EEG evaluation of the R(-) isomer revealed less overall slowing and an absence of the large slow wave complexes produced by the S(+) isomer and the racemic mixture. The pharmacokinetic profiles for the individual isomers of ketamine did not differ significantly from the racemic mixture. Even though the apparent anesthetic state produced in these healthy volunteers did not differ qualitatively between the 3 drug groups, recovery times (assessed using a standardized battery of psychometric tests) were consistently shorter following the individual isomers than with the racemic mixture. The serum ketamine concentrations associated with regaining consciousness and orientation were consistent with an S(+):R(-) isomer potency ratio of 4:1. In terms of their ability to impair psychomotor function, the S(+):R(-) potency ratio varied from 3:1-5:1. After comparable degrees of CNS depression, the more potent S(+) isomer of ketamine was associated with a more rapid recovery of psychomotor skills than the currently used racemic mixture.