Cerebrospinal fluid and plasma pharmacokinetics of the cyclooxygenase 2 inhibitor rofecoxib in humans: single and multiple oral drug administration.
Anesth Analg
; 100(5): 1320-1324, 2005 May.
Article
en En
| MEDLINE
| ID: mdl-15845677
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sulfonas
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Inhibidores de la Ciclooxigenasa
/
Lactonas
Tipo de estudio:
Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Anesth Analg
Año:
2005
Tipo del documento:
Article
País de afiliación:
Canadá