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


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.


CONCLUSIONS
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.
Goldberg
Michael E
ME
Cooper University Hospital, Department of Anesthesiology, UMDNJ-Robert Wood Johnson Medical School, Camden, New Jersey, USA. Goldberg-Mike@Cooperhealth.edu
Torjman
Marc C
MC
Schwartzman
Robert J
RJ
Mager
Donald E
DE
Wainer
Irving W
IW
D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002853:Chromatography, Liquid; D020918:Complex Regional Pain Syndromes / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000700:Analgesics; D007649:Ketamine; C033419:norketamine
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