DOSAGE PREDICTIONS IN HIGH-DOSE METHOTREXATE INFUSIONS .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 errror : rmse (precision) = 1.14 l .cntdot. h-1 (11.2%) and mean error : me (bias)=0.06 l .cntdot. h-1 (NS) relatively to weighted least-square estimates, n=50). The precision of Bayesian prediction was comparable to that of the independent model which is used in routine practice and involves 9 measured levels over 30 h, (rmse = 1.35 l .cntdot. h-1 (10.9%), n = 50). However, the routine method presented a significant bias (me = -0.81 1.cntdot.h-1, n = 50).