7-hydroxymethotrexate and Nausea

Drugs prescribed for rheumatoid arthritis are often associated with gastrointestinal toxicity, and proton pump inhibitors may be coadministered for gastroprotection. In this open-label study, the effect of lansoprazole 30 mg qd and naproxen 500 mg bid on the pharmacokinetic profile of methotrexate was investigated. Twenty-seven adult rheumatoid arthritis patients on stable oral methotrexate doses (7.5-15 mg/week) for a minimum of 3 months were enrolled. Methotrexate pharmacokinetics were assessed on days -1 (methotrexate alone) and 7 (methotrexate with lansoprazole and naproxen). Pharmacokinetics of methotrexate and 7-hydroxymethotrexate were not altered by coadministration of methotrexate with lansoprazole and naproxen; point estimates and 90% confidence intervals for the peak plasma concentration and area under the plasma concentration-time curve of methotrexate and 7-hydroxymethotrexate were within the 0.80 to 1.25 boundaries. Therefore, coadministration of naproxen and lansoprazole for 7 days does not affect the pharmacokinetic profile of low doses of methotrexate.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Area Under Curve; Arthritis, Rheumatoid; Dizziness; Dose-Response Relationship, Drug; Female; Headache; Humans; Lansoprazole; Male; Metabolic Clearance Rate; Methotrexate; Middle Aged; Naproxen; Nausea; Omeprazole; Vomiting