Total and free methotrexate pharmacokinetics in elderly patients with rheumatoid 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 pharmacokinetic data to those in patients 21 to 45 years of age.


METHODS
Thirty-eight elderly patients (8 men, 30 women) and 24 young patients (6 men, 18 women) underwent this pharmacokinetic study. They received intramuscular administration of MTX each week, at a dose varying from 7.5 to 15 mg depending on the patient. MTX concentrations in plasma and ultrafiltrate samples were assayed by a fluorescence polarization immunoassay. Pharmacokinetic variables were estimated using a Bayesian approach with population parameters as a priori information together with 2 plasma MTX concentrations (2 and 8 h after injection).


RESULTS
The extent of unbound fraction and the volume of distribution were not statistically significantly different between the 2 age groups. The elimination 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).


CONCLUSIONS
MTX clearance 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.
Bressolle
F
F
Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Montpellier, France.
Bologna
C
C
Kinowski
J M
JM
Arcos
B
B
Sany
J
J
Combe
B
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged
D003404:Creatinine; D008727:Methotrexate