BAYESIAN CALCULATION OF METHOTREXATE CLEARANCE AFTER LOW-DOSE INTRAMUSCULAR ADMINISTRATION IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective. To determine a pharmacokinetic procedure (Bayesian method) for estimation of methotrexate (MTX) clearance, using only 2 blood sam ples, in outpatients with rheumatoid arthritis treated with low dose i ntramuscular (im) MTX. Methods. Population pharmacokinetic parameters were obtained by.the weighted least squares (WLSQ) method in plasma sa mples from 14 patients with rheumatoid arthritis (RA). In each patient , 1.1 samples were measured by fluorescence polarization immunoassay, at Time 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12, and 24 h after im admin istration. These measures were validated by pharmacokinetic studies in 20 other patients with RA. Individual total body clearance of MTX was calculated using only 2 plasma samples (at 0.5 and 2 h after im injec tion) by the Bayesian method using the population pharmacokinetic para meters. The clearance measures obtained by the Bayesian method were co mpared with those obtained by the WLSQ method. Results, The pharmacoki netic variables (clearance, half-life, area under the curve) of 14 pat ients were determined, as well as the covariance and the mean values n ecessary to apply the Bayesian method. No significant difference was f ound between clearance values obtained by the Bayesian method compared to the WLSQ method, confirming the validity of the Bayesian values. C onclusion. The present population pharmacokinetic parameters allowed t he determination of individual clearance of MTX with only 2 plasma sam ples (0.5 and 2 h after administration) in patients treated with low d ose im MTX. Individual clearance is used to modulate MTX administratio n in patients presenting adverse reactions in spite of good clinical r esponse. Individual determination of MTX pharmacokinetics in patients at risk for adverse MTX reactions could be useful for adjustment of th e drug regimen.