Enantioselective pharmacokinetics of (R)- and (S)-ketamine after a 5-day infusion in patients with complex regional pain syndrome.

Abstract

INTRODUCTION:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Michael E Goldberg, Marc C Torjman, Robert J Schwartzman, Donald E Mager, Irving W Wainer
• Journal: Chirality (Chirality) Vol. 23 Issue 2 Pg. 138-43 (Feb 2011) ISSN: 1520-636X [Electronic] United States
• PMID: 20803495 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2010 Wiley-Liss, Inc.

Chemical References

• Analgesics
• Ketamine
• norketamine

Topics

• Adolescent
• Adult
• Analgesics (blood, pharmacokinetics, therapeutic use)
• Chromatography, Liquid
• Complex Regional Pain Syndromes (drug therapy)
• Female
• Humans
• Infusions, Intravenous
• Ketamine (analogs & derivatives, blood, pharmacokinetics, therapeutic use)
• Male
• Mass Spectrometry
• Middle Aged
• Stereoisomerism
• Structure-Activity Relationship
• Time Factors
• Treatment Outcome
• Young Adult