Pharmacokinetics of factor VIII in hemophilia A patients assessed by frequency response method

The frequency response method, having its mathematical underpinnings in the theory of linear dynamic systems, was utilized to model pharmacokinetic systems describing the fate of factor VIII (F VIII) administered to hemophilia A patients before surgery. The pharmacokinetic system was defined on the basis of the patient's data in such a way that the injection of F VIII during 5-15 min was considered the input, and the corresponding plasma F VIII concentration profile consisting of both the injection and post-injection part the output of this system. The approach is an alternative to routine procedures based only on evaluation of the post-injection part of the F VIII concentration profile. With respect to the common sampling schedule of F VIII, simple second-order models were found acceptable for all the patients involved in the study. However, in the patients whose plasma F VIII concentration profiles did not decrease monotonously after the injection, these models failed to approximate secondary peaks indicating the presence of time delays in F VIII kinetics. The results obtained were discussed with respect to applications of pharmacokinetic models for the adjusted dose continuous infusion of F VIII in hemophilia A patients during and after surgical interventions.