静脉注射后志愿者体内丙胺卡因的药代动力学：对映体选择性。

Pharmacokinetics of prilocaine after intravenous administration in volunteers: enantioselectivity.

作者信息

van der Meer A D, Burm A G, Stienstra R, van Kleef J W, Vletter A A, Olieman W

机构信息

Department of Anesthesiology, Leiden University Medical Center, The Netherlands.

出版信息

Anesthesiology. 1999 Apr;90(4):988-92. doi: 10.1097/00000542-199904000-00010.

DOI:10.1097/00000542-199904000-00010

PMID:10201668

Abstract

BACKGROUND

Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous administration of the racemate.

METHODS

Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis.

RESULTS

The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P < 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma clearance of R(-)-prilocaine (2.57+/-0.46 l/min) was larger (P < 0.0001) than that of S(+)-prilocaine (1.91+/-0.30 l/min). The steady-state volume of distribution of R(-)-prilocaine (279+/-94 l) did not differ from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (87+/-27 min) was shorter (P < 0.05) than that of S(+)-prilocaine (124+/-64 min), as was the mean residence time of R(-)-prilocaine (108+/-30 min) compared with S(+)-prilocaine (155+/-59 min; P < 0.005).

CONCLUSIONS

The pharmacokinetics of prilocaine are enantioselective. The difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.

摘要

背景

丙胺卡因存在两种立体异构构型，即对映体S(+)-丙胺卡因和R(-)-丙胺卡因。该药物临床使用的是外消旋体。本研究考察了静脉注射外消旋体后对映体的药代动力学。

方法

10名健康男性志愿者接受200mg外消旋丙胺卡因，静脉输注10分钟。输注开始后8小时采集血样。采用立体选择性高效液相色谱法（HPLC）测定血浆浓度。使用平衡透析法测定在加入外消旋丙胺卡因的空白血样中对映体的游离分数。

结果

R(-)-丙胺卡因的游离分数（均值±标准差，70%±8%）低于S(+)-丙胺卡因（73%±5%）（P<0.05）。R(-)-丙胺卡因的总血浆清除率（2.57±0.46 l/min）高于S(+)-丙胺卡因（1.91±0.30 l/min）（P<0.0001）。R(-)-丙胺卡因的稳态分布容积（279±94 l）与S(+)-丙胺卡因（291±93 l）无差异。R(-)-丙胺卡因的终末半衰期（87±27分钟）短于S(+)-丙胺卡因（124±64分钟）（P<0.05），R(-)-丙胺卡因的平均驻留时间（108±30分钟）也短于S(+)-丙胺卡因（155±59分钟；P<0.005）。