IMPROVED COST-EFFECTIVENESS BY PHARMACOKINETIC DOSING OF FACTOR-VIII IN PROPHYLACTIC TREATMENT OF HAEMOPHILIA-A

The aim of the study was to investigate the feasibility of optimizing prophylactic dosing of factor VIII by the use of individual pharmacoki netic data. Twenty-one patients were enrolled in a randomized cross-ov er study on standard dosage regimens vs dosing according to pharmacoki netic principles. The study period was 2x6 months. Using single-dose p harmacokinetic data for each patient, plasma factor VIII procoagulant activity (FVIII:C) curves following various doses and intervals were c omputer-simulated. From these calculations, a suitable dosage was chos en. FVIII:C was also repeatedly measured during study periods. Trough levels of FVIII:C, numbers of spontaneous joint bleedings and amounts of factor concentrate used during the two study periods were compared for each patient. There was a close correlation between predicted and measured values of FVIII:C. As the half-lives of FVIII:C in the patien ts varied from 7.8 to 18.3 h, it was obviously beneficial to base the dosage on individual pharmacokinetic data. Fourteen patients completed both study periods. Mean trough level exogenous FVIII:C was raised fr om 0.89 (SD 0.73) U dl(-1) during pharmacokinetic dosage. Concomitantl y, mean 6-month consumption factor VIII was decreased from 124000 (SD 30000) units to 84000 (31000) units. Numbers of reported bleedings wer e generally similar during both periods. The study demonstrates the us efulness of individual pharmacokinetics as a tool for cost-effective u tilization of factor VIII in the prophylactic treatment of haemophilia A.