title: Coadministration of lansoprazole and naproxen does not affect the pharmacokinetic profile of methotrexate in adult patients with rheumatoid arthritis.
abstract: 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.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, TAP Pharmaceutical Products Inc., 675 North Field Drive, Lake Forest, IL 60045, USA. majid.vakily@tap.com
authors.forename: Majid
authors.initials: M
authors.lastname: Vakily
authors.forename: Fouad
authors.initials: F
authors.lastname: Amer
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kukulka
authors.forename: Nupun
authors.initials: N
authors.lastname: Andhivarothai
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D004244:Dizziness / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D006261:Headache / Q000139:chemically induced; D006801:Humans; D064747:Lansoprazole; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D009325:Nausea / Q000139:chemically induced; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D014839:Vomiting / Q000139:chemically induced
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D064747:Lansoprazole; D009288:Naproxen; D009853:Omeprazole; C011864:7-hydroxymethotrexate; D008727:Methotrexate