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Examination of the effect of increasing doses of etoricoxib on oral methotrexate pharmacokinetics in patients with rheumatoid arthritis.
- Source :
-
Journal of clinical pharmacology [J Clin Pharmacol] 2009 Oct; Vol. 49 (10), pp. 1202-9. - Publication Year :
- 2009
-
Abstract
- The authors designed 2 randomized controlled studies to examine the effects of etoricoxib 60 to 120 mg daily on methotrexate pharmacokinetics in 50 rheumatoid arthritis (RA) patients on stable doses of methotrexate (7.5-20 mg). Patients received oral methotrexate at baseline and on days 7 and 14. In study 1, patients received etoricoxib 60 mg (days 1-7) and then 120 mg (days 8-14); in study 2, patients received etoricoxib 90 mg (days 1-7) and then 120 mg (days 8-14). For study 1, the AUC(0-infinity) geometric mean ratio (GMR) (90% confidence interval [CI]) for day 7 versus baseline was 1.01 (0.91, 1.12) for etoricoxib 60 mg; the area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) GMR (90% CI) for day 14 was 1.28 (1.15, 1.42) for etoricoxib 120 mg. For study 2, the AUC(0-infinity) GMR (90% CI) for day 7 versus baseline was 1.07 (1.01, 1.13) for etoricoxib 90 mg; the AUC(0-infinity) GMR (90% CI) for day 14 was 1.05 (0.99, 1.11) for etoricoxib 120 mg. In summary, etoricoxib 60 and 90 mg had no effect on methotrexate plasma concentrations. Although no effect on methotrexate pharmacokinetics was observed with etoricoxib 120 mg in study 2, GMR AUC(0-infinity) fell outside the prespecified bounds in study 1. Standard monitoring of methotrexate-related toxicity should be continued when etoricoxib and methotrexate are administered concurrently, especially with doses >90 mg etoricoxib.
- Subjects :
- Administration, Oral
Adult
Aged
Antirheumatic Agents administration & dosage
Arthritis, Rheumatoid drug therapy
Cyclooxygenase 2 Inhibitors administration & dosage
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Interactions
Etoricoxib
Female
Humans
Male
Methotrexate administration & dosage
Middle Aged
Pyridines administration & dosage
Sulfones administration & dosage
Antirheumatic Agents pharmacokinetics
Cyclooxygenase 2 Inhibitors adverse effects
Drug Therapy, Combination adverse effects
Methotrexate pharmacokinetics
Pyridines adverse effects
Sulfones adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4604
- Volume :
- 49
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19783714
- Full Text :
- https://doi.org/10.1177/0091270009338939