Single-dose pharmacokinetics of factor IX evaluated by model-independent methods

We studied the pharmacokinetic data of 13 subjects with hemophilia B treated with a single-dose of a Factor IX concentrate (Bebulin TIM2, N = 9; Preconativ, N = 4). The decay curves of Factor IX were evaluated by model-independent methods and the following pharmacokinetic parameters (mean +/- SD) were estimated: clearance (ml/h/kg) = 4.99 +/- 2.01; mean residence time (h) = 22.9 +/- 10.6; volume of distribution (ml/kg) = 99.9 +/- 35.5. The in vivo recovery (59.8% +/- 16.9%) was found to be inversely correlated with the volume of distribution. No significant difference in the pharmacokinetic parameters was found between patients treated with Preconativ and those treated with Bebulin. A model-dependent compartmental evaluation of the 13 decay curves showed that the two-compartment model was better than the one-compartment model in 7 cases (53.8%), but the improvement of fit resulting from the two-compartment model was statistically significant in only 2 cases (15.4%).