TOTAL AND FREE METHOTREXATE PHARMACOKINETICS IN ELDERLY PATIENTS WITHRHEUMATOID-ARTHRITIS - A COMPARISON WITH YOUNG-PATIENTS

Objective. To determine the pharmacokinetics of methotrexate (MTX) in a group of patients 65 to 83 years of age and to compare the pharmacok inetic data to those in patients 21 to 45 years of age, Methods, Thirt y-eight elderly patients (8 men, 30 women) and 21 young patients (6 me n, 18 women) underwent this pharmacokinetic study. They received intra muscular administration of MTX each week, at a dose varying from 7.5 t o 15 mg depending on the patient, MTX concentrations in plasma and ult rafiltrate samples were assayed by a fluorescence polarization immunoa ssay. Pharmacokinetic variables were estimated using a Bayesian approa ch with population parameters as a priori information together with 2 plasma MTX concentrations (2 and 8 h after injection). Results, The ex tent of unbound fraction and the volume of distribution were not stati stically significantly different between the 2 age groups, The elimina tion half-life measures of the free and total MTX were greatest in the elderly group (p < 0.001). The total clearances of free and total MTX were inversely proportional to age (p < 0.001), Conclusion. MTX clear ance decreases with decreasing creatinine clearance and smaller doses may be chosen in this group. Thus, a dosage regimen should be adjusted in elderly patients or in those with renal impairment.