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Anesth Analg 2005;100:1320-1324
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000150597.94682.85

ANESTHETIC PHARMACOLOGY

Cerebrospinal Fluid and Plasma Pharmacokinetics of the Cyclooxygenase 2 Inhibitor Rofecoxib in Humans: Single and Multiple Oral Drug Administration

Asokumar Buvanendran, MD*, Jeffrey S. Kroin, PhD*, Kenneth J. Tuman, MD*, Timothy R. Lubenow, MD*, Dalia Elmofty, MD*, and Pauline Luk, BS{dagger}

*Department of Anesthesiology, Rush Medical College at Rush University Medical Center, Chicago, Illinois; and {dagger}Merck Frosst Canada, Kirkland, Quebec, Canada

Address correspondence and reprint requests to Asokumar Buvanendran, MD, Department of Anesthesiology, 1653 W. Congress Pkwy., Rush University Medical Center, Chicago, IL 60612. Address e-mail to Asokumar{at}aol.com.

Cerebrospinal fluid (CSF) pharmacokinetics of orally administered cyclooxygenase 2 inhibitors, with single or multiple dosing, is of clinical relevance because it may relate to the analgesic efficacy of these drugs. We enrolled 9 subjects with implanted intrathecal catheters in the study. After 50-mg oral rofecoxib administration, the CSF drug concentration lagged slightly behind the plasma drug concentration. The ratio of the 24-h area under the drug-concentration curve (AUC) in CSF to plasma was 0.142. After daily dosing of rofecoxib 50 mg/d for 9 days, rofecoxib concentrations in plasma and CSF were larger on Day 9 than on Day 1, with the 24-h AUC on Day 9 more than twice the Day 1 AUC for both plasma and CSF. After nine consecutive daily doses of rofecoxib, the AUCCSF/AUCplasma ratio was 0.159. The important findings of this study are that CSF rofecoxib levels are approximately 15% of plasma levels and that repeated daily dosing more than doubles the AUC in CSF.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2005 by the International Anesthesia Research Society.