Cerebrospinal fluid and plasma pharmacokinetics of the cyclooxygenase 2 inhibitor rofecoxib in humans: single and multiple oral drug administration.
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 AUC(CSF)/AUC(plasma) 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.
Buvanendran
Asokumar
A
*Department of Anesthesiology, Rush Medical College at Rush University Medical Center, Chicago, Illinois; and †Merck Frosst Canada, Kirkland, Quebec, Canada.
Kroin
Jeffrey S
JS
Tuman
Kenneth J
KJ
Lubenow
Timothy R
TR
Elmofty
Dalia
D
Luk
Pauline
P
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016861:Cyclooxygenase Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D013450:Sulfones / Q000008:administration & dosage / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib