Multi-variate analysis of factors governing the pharmacokinetics of exogenous factor VIII in haemophiliacs |
| |
Authors: | A Messori G Longo M Morfini S Cinotti E Filimberti G Giustarini P Rossi Ferrini |
| |
Institution: | (1) Haemophilia Centre, USL 10/D, and University of Florence, Florence, Italy |
| |
Abstract: | Summary The pharmacokinetics of Factor VIII was evaluated by mathematical modeling in a large-scale study in 62 haemophilia-A subjects, in whom 137 plasma Factor VIII-time curves were measured during single dose (n=87) and repeated-dose (n=47) treatments for prophylaxis or minor bleeding episodes. The pharmacokinetic parameters mean (SD)] estimated from single-dose curves were: clearance 3.85 ml·h–1·kg–1, volume of distribution 58.2 ml·kg–1, mean residence time 15.9 h. Parameters calculated from repeated-dose curves were: clearance 3.93 ml·h–1·kg–1, volume of distribution 61.8 ml·kg–1, and half-life 12.2 h. In patients with mild haemophilia, pharmaco-statistical analysis revealed that the endogenous synthesis of Factor VIII was constant and was not influenced by the administration of exogenous Factor VIII. The coefficient of variation for intra-individual variability of Factor VIII kinetics (estimated according to the Standard Two-Stage method) was 20.7% in single-dose curves and 23.2% in repeated-dose curves. |
| |
Keywords: | haemophilia-A factor VIII pharmacokinetics |
本文献已被 SpringerLink 等数据库收录! |
|