Enantioselective pharmacokinetics of (R)‐ and (S)‐ketamine after a 5‐day infusion in patients with complex regional pain syndrome |
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Authors: | Michael E Goldberg Marc C Torjman Robert J Schwartzman Donald E Mager Irving W Wainer |
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Institution: | 1. Cooper University Hospital, Department of Anesthesiology, UMDNJ‐Robert Wood Johnson Medical School, Camden, New Jersey;2. Department of Neurology, Drexel University College of Medicine, Philadelphia, Pennsylvania;3. Department of Pharmaceutical Sciences, The University of Buffalo, Buffalo, New York;4. Bioanalytical Chemistry and Drug Discovery Section, Laboratory of Clinical Investigation, National Institute on Aging Intramural Research Program, Baltimore, Maryland |
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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. Chirality, 2011. © 2010 Wiley‐Liss, Inc. |
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Keywords: | ketamine norketamine CRPS pharmacokinetics pharmacodynamics enantioselective liquid chromatography mass spectrometry |
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