Lack of Pharmacokinetic Interaction between Rofecoxib and Methotrexate in Rheumatoid Arthritis Patients
| Autor: | Arturo G. Porras, Jutta L. Miller, David L. Ebel, J. S. Redfern, Gregory B. Holmes, Nancy G. B. Agrawal, Marshall Sack, Jules I. Schwartz, Barry J. Gertz, Kenneth Bachmann, Peggy H. Wong |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Male medicine.medical_specialty Cmax Arthritis Pharmacology Placebo Gastroenterology Arthritis Rheumatoid Lactones chemistry.chemical_compound Double-Blind Method Pharmacokinetics Internal medicine Confidence Intervals medicine Humans Cyclooxygenase Inhibitors Drug Interactions Pharmacology (medical) Sulfones Rofecoxib Aged Analysis of Variance Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Methotrexate chemistry Antirheumatic Agents Area Under Curve Rheumatoid arthritis Antifolate Folic Acid Antagonists Female business medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 41:1120-1130 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/00912700122012616 |
| Popis: | Rofecoxib is a highly selective and potent inhibitor of cyclooxgenase-2 (COX-2). Methotrexate is a disease-modifying agent with a narrow therapeutic index frequently prescribed for the management of rheumatoid arthritis. The objective of this study was to investigate the influence of clinical doses of rofecoxib on the pharmacokinetics of methotrexate in patients with rheumatoid arthritis. This was a randomized, double-blind, placebo-controlled study in 25 rheumatoid arthritis patients on stable doses of methotrexate. Patients received oral methotrexate (7.5 to 20 mg) on days -1, 7, 14, and 21. Nineteen patients received rofecoxib 12.5, 25, and 50 mg once daily on days 1 to 7, 8 to 14, and 15 to 21, respectively. Six patients received placebo on days 1 to 21 only to maintain a double-blinded design for assessment of adverse experiences. Plasma and urine samples were analyzed for methotrexate and its major although inactive metabolite, 7-hydroxymethotrexate. The AUC(0-infinity) geometric mean ratios (GMR) and their 90% confidence intervals (90% CI) (rofecoxib + methotrexate/methotrexate alone) for day 7/day -1, day 14/day -1, and day 21/day -1, for rofecoxib 12.5, 25, and 50 mg, were 1.03 (0.93, 1.14), 1.02 (0.92, 1.12), and 1.06 (0.96, 1.17), respectively (p > 0.2 for all comparisons to day -1). All AUC(0-infinity), GMR and Cmax GMR 90% CIs fell within the predefined comparability limits of (0.80, 1.25). Similar results were observed for renal clearance of methotrexate and 7-hydroxymethotrexate at the highest dose of rofecoxib tested (50 mg). It was concluded that rofecoxib at doses of 12.5, 25, and 50 mg once daily has no effect on the plasma concentrations or renal clearance (tested at the highest dose of rofecoxib) of methotrexate in rheumatoid arthritis patients. |
| Databáze: | OpenAIRE |
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