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Ann Rheum Dis 1998;57:110-113 ( February )

Concise reports

Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients F Bressolle,a C Bologna,b J M Kinowski,a J Sany,b B Combeb

a Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Montpellier, and Laboratoire de Pharmacocinétique, CHU Carémeau, Nîmes, France, b Fédération de Rhumatologie, CHU Lapeyronie, Montpellier, France

Correspondence to: Professor B Combe, Fédération de Rhumatologie, CHU Lapeyronie, 34295 Montpellier Cedex 5, France.

Accepted for publication 6 January 1998

OBJECTIVES---To determine the effects of impaired renal function on the pharmacokinetics of methotrexate (MTX) in rheumatoid arthritis (RA) patients.
METHODS---77 RA patients were included in this study. MTX was administered intramuscularly (7.5 to 15 mg). Subjects were divided into four groups, according to their creatinine clearance (CLCR); group 1: CLCR lower than 45 ml/min; group 2: CLCR between 45 and 60 ml/min, group 3: CLCR between 61 and 80 ml/min and group 4: CLCR higher than 80 ml/min. Blood samples were collected from each subject before drug administration and at two and eight hours after administration. Individual pharmacokinetic parameters were estimated using a Bayesian approach.
RESULTS---MTX concentrations (total and free) were 1.3 to 1.6-times higher in group 1 than in groups 2, 3, and 4. For total and free MTX, t1/2 eliminations were 22.7 hours in group 1, 13.5 hours in group 2, 12 hours in group 3, and 11 hours in group 4. Clearance of total MTX was 64, 92, 96, 115 ml/min in groups 1 to 4, respectively, it was 118, 163, 171, 206 ml/min in groups 1 to 4 for the free MTX, respectively. Volume of distribution averaged 2.16 l/kg in group 1, 1.92 l/kg in group 2, 1.61 l/kg in group 3, and 1.56 l/kg in group 4. Elimination half life was significantly increased and total clearance was significantly reduced with the degree of renal impairment. Linear regression revealed good correlations between clearance values of MTX and creatinine clearance.
CONCLUSION---Individual testing is required rather than a general decrease of the MTX dose based only on CLCR.

Keywords: rheumatoid arthritis; methotrexate; renal insufficiency

© 1998 by Annals of the Rheumatic Diseases


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