Pharmacokinetics of Prilocaine after Intravenous Administration in VolunteersEnantioselectivity
作者:
Auke van der Meer,
Anton Burm,
Rudolf Stienstra,
Jack van Kleef,
Arie Vletter,
Wim Olieman,
期刊:
Anesthesiology
(OVID Available online 1999)
卷期:
Volume 90,
issue 4
页码: 988-992
ISSN:0003-3022
年代: 1999
出版商: OVID
关键词: Chiral drugs;protein binding;toxicity.
数据来源: OVID
摘要:
BackgroundPrilocaine 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.MethodsTen 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.ResultsThe 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).ConclusionsThe pharmacokinetics of prilocaine are enantio‐selective. 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.
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