Dosage Predictions in High-Dose Methotrexate Infusions Part 2: Bayesian Estimation of Methotrexate Clearance

Population pharmacokinetics of methotrexate (MTX) was evaluated from intravenous test-dose (TD) data (n=20 corresponding to 174 measured samples).

Bayesian prediction of MTX clearance from TD experiments combining population data with measured levels (at times 0.5 and 6 h) was found to be feasible in routine situations with good performance (root mean squared error: rmse (precision) = 1.14 l.h^-1 (11.2 %) and mean error: me (bias)=0.06 l.h^-1 (NS) relatively to weighted least-square estimates, n=50).

The precision of Bayesian prediction was comparable to that of the model independent which is used in routine practice and involves 9 measured levels over 30 h, (rmse = 1.35 l.h^-1 (10.9 %), n=50). However, the routine method presented a significative bias (me = - 0.81 l.h^-1, n = 50).