Pharmacokinetics and renal function in patients with rheumatoid arthritis receiving a standard dose of oral weekly methotrexate: association with significant decreases in creatinine clearance and renal clearance of the drug after 6 months of therapy.

OBJECTIVE

To determine the pharmacokinetics of a standard oral dose of 7.5 mg in a cohort of patients beginning methotrexate (MTX) and continuing the drug over 24 months.

METHODS

Twenty-one patients underwent pharmacokinetic testing after receiving a dose of 7.5 mg of oral MTX and concomitant nonsteroidal antiinflammatory drug (NSAID) therapy. Studies were performed at the time of MTX initiation, and after 6 and 24 months of therapy.

RESULTS

No significant differences with time were observed in area under the serum concentration versus time curve (AUC), maximal MTX concentration achieved postdosing (Cmax) or time to maximal MTX concentration (Tmax). Renal clearance of MTX at 6 months decreased by a mean (+/- SD) of 23.8 (40.3) cc/min (p = 0.014). Creatinine clearance decreased by 8.6 cc/min (17.2) (p = 0.033) at 6 months.

CONCLUSION

No differences in AUC, Tmax, or Cmax were observed over a 2 year period in patients with rheumatoid arthritis on a standard 7.5 mg dose of MTX. Renal clearance and creatinine clearance both decreased significantly after 6 months of treatment. This effect may be clinically relevant in certain individuals as MTX is renally excreted.