Multi-variate analysis of factors governing the pharmacokinetics of exogenous factor VIII in haemophiliacs.
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.
Messori
A
A
Haemophilia Centre, University of Florence, Italy.
Longo
G
G
Morfini
M
M
Cinotti
S
S
Filimberti
E
E
Giustarini
G
G
Rossi Ferrini
P
P
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006467:Hemophilia A / Q000097:blood*; D006801:Humans; D007223:Infant; D008875:Middle Aged; D013223:Statistics as Topic
D005169:Factor VIII