ABSTRACT
Febuxostat is a novel nonpurine selective inhibitor of xanthine oxidase, which is currently being developed for the management of hyperuricemia in patients with gout. The effect of age and gender on the pharmacokinetics, pharmacodynamics, and safety of once-daily oral febuxostat 80 mg was assessed in healthy male and female subjects after 7 days. Following multiple dosing with febuxostat, there were no statistically significant differences in the plasma or urinary pharmacokinetic or pharmacodynamic parameters between subjects aged 18 to 40 years and >or=65 years. Although unbound peak concentration (C(max,u)) and area under the concentration-time curve (AUC(24,u)) for febuxostat were higher in women as compared with men (31.5 vs 23.6 ng/mL, P Subject(s)
Enzyme Inhibitors/pharmacokinetics
, Gout Suppressants/pharmacokinetics
, Thiazoles/pharmacokinetics
, Xanthine Oxidase/antagonists & inhibitors
, Administration, Oral
, Adolescent
, Adult
, Age Factors
, Aged
, Biotransformation
, Enzyme Inhibitors/administration & dosage
, Enzyme Inhibitors/adverse effects
, Febuxostat
, Female
, Gout Suppressants/administration & dosage
, Gout Suppressants/adverse effects
, Humans
, Hypoxanthine/blood
, Male
, Protein Binding
, Sex Factors
, Thiazoles/administration & dosage
, Thiazoles/adverse effects
, Uric Acid/blood
, Xanthine/blood
, Young Adult
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.
