Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine

Citation
H. Ihmsen et al., Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine, CLIN PHARM, 70(5), 2001, pp. 431-438
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOLOGY & THERAPEUTICS
ISSN journal
0009-9236 → ACNP
Volume
70
Issue
5
Year of publication
2001
Pages
431 - 438
Database
ISI
SICI code
0009-9236(200111)70:5<431:SPOKRI>2.0.ZU;2-A
Abstract
Objective: We investigated the pharmacokinetics of ketamine with special re gard to enantiomer-specific differences. Methods. Ten healthy young male volunteers (mean age, 28 +/- 4 years; mean weight, 79 +/- 11 kg) received racemic ketamine and S(+)-ketamine in a rand omized double-blind crossover study. Drugs were administered by a computer- controlled device. Two infusion cycles with linearly increasing targets [sl ope, 0.1 mug (.) ml(-1) (.) min(-1) for S(+)-ketamine and 0.2 mug (.) ml(-1 ) (.) min(-1) for racemic ketamine] were administered. Concentrations of th e ketamine enantiomers were determined from arterial blood, and pharmacokin etic parameters were estimated with a 2- and 3-compartment model. Results: The total doses needed to reach defined end points were 271 +/- 80 mg and 409 +/- 75 mg for S(+)ketamine and racemic ketamine, respectively ( P < .05). S(+)-ketamine showed a significantly higher clearance (26.3 +/- 3 .5 ml (.) kg(-1) (.) min(-1)) compared with racemic ketamine (14.8 +/- 1.7 ml (.) kg(-1) (.) min(-1); P < .05) and R(-)-ketamine (13.8 +/- 1.3 ml (.) kg(-1) (.) min(-1); P < .05). Furthermore, the clearance of the S(+)-ketami ne was smaller in the racemate (18.5 +/- 0.7 ml (.) kg(-1) (.) min(-1); P < .05) than for the pure isomer. Conclusions: These results demonstrate that R(-)-ketamine inhibits the elim ination of S(+)-ketamine.