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Journal article
Enantioselective pharmacokinetics of (R)- and (S)-ketamine after a 5-day infusion in patients with complex regional pain syndrome
Chirality (New York, N.Y.), v 23(2)
Feb 2011
PMID: 20803495
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Abstract
This study determined the pharmacokinetics and pharmacodynamics of (R)- and (S)-ketamine and (R)- and (S)-norketamine following a 5-day moderate dose, as a continuous (R,S)-ketamine infusion in complex regional pain syndrome (CRPS) patients.
Ketamine was titrated to 10-40 mg/h and maintained for 5 days. (R)- and (S)-Ketamine and (R)- and (S)-norketamine pharmacokinetic and pharmacodynamic studies were performed. Blood samples were obtained on Day 1 preinfusion, and at 60-90, 120-150, 180-210, and 240-300 min after the start of the infusion, on Days 2, 3, 4, 5, and on Day 5 at 60 min after the end of infusion. The plasma concentrations of (R)- and (S)-ketamine and (R)- and (S)-norketamine were determined using enantioselective liquid chromatography-mass spectrometry.
Ketamine and norketamine levels stabilized 5 h after the start of the infusion. (R)-Ketamine clearance was significantly lower resulting in higher steady-state plasma concentrations than (S)-ketamine. The first-order elimination for (S)-norketamine was significantly greater than that of (R)-enantiomer. When comparing the pharmacokinetic parameters of the patients who responded to ketamine treatment with those who did not, no differences were observed in ketamine clearance and the first-order elimination of norketamine.
The results indicate that (R)- and (S)-ketamine and (R)- and (S)-norketamine plasma concentrations do not explain the antinociceptive activity of the drug in patients suffering from CRPS.
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Details
- Title
- Enantioselective pharmacokinetics of (R)- and (S)-ketamine after a 5-day infusion in patients with complex regional pain syndrome
- Creators
- Michael E Goldberg - Cooper University HospitalMarc C Torjman - Cooper University HospitalRobert J Schwartzman - Drexel UniversityDonald E Mager - University at Buffalo, State University of New YorkIrving W Wainer - Bioanalytical Chemistry and Drug Discovery Section, Laboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, Baltimore, Maryland
- Publication Details
- Chirality (New York, N.Y.), v 23(2)
- Publisher
- Wiley
- Grant note
- R01 GM057980 / NIGMS NIH HHS Intramural NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurology
- Web of Science ID
- WOS:000285976800008
- Scopus ID
- 2-s2.0-78650949485
- Other Identifier
- 991019167844804721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Analytical
- Chemistry, Medicinal
- Chemistry, Organic
- Pharmacology & Pharmacy