Pharmacokinetics of a New Heat-treated Concentrate of Factor VIII Estimated by Model-independent Methods

We evaluated the pharmacokinetic properties of Kryobulin TIM3, a new heat-treated Factor VIII concentrate which has recently become available in Europe. Twelve patients with classic hemophilia were studied. In each patient, Factor VIII was given as a single dose (ranging from 11.6 to 30.3 units/kg) after which eight serial blood samples were drawn to characterize the disappearance of Factor VIII from the plasma. Model-independent (noncompartmental) methods were used for pharmacokinetic analysis. The following pharmacokinetic parameters of Factor VIII (mean +/- SD) were estimated: clearance = 3.83 +/- 0.99 ml/h/kg; mean residence time = 15.9 +/- 4.5 h; volume of distribution at steady state = 55.6 +/- 9.3 ml/kg; in-vivo recovery = 129 +/- 29%. The pharmacokinetic parameters of Kryobulin TIM3 obtained in our study are very similar to those previously reported for the untreated concentrate. Thus, our findings suggest that the dosing guidelines previously available for the untreated concentrate need not be revised when using the treated product.