title: Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight.
abstract: Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half-life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PK-based dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling.
authors: Department of Pharmaceutical Biosciences, Uppsala University, Sweden. sven.bjorkman@farmbio.uu.se
authors: Sven
authors: S
authors: Björkman
authors: MyungShin
authors: M
authors: Oh
authors: Gerald
authors: G
authors: Spotts
authors: Phillip
authors: P
authors: Schroth
authors: Sandor
authors: S
authors: Fritsch
authors: Bruce M
authors: BM
authors: Ewenstein
authors: Kathleen
authors: K
authors: Casey
authors: Kathelijn
authors: K
authors: Fischer
authors: Victor S
authors: VS
authors: Blanchette
authors: Peter W
authors: PW
authors: Collins
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006467:Hemophilia A / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012189:Retrospective Studies; D014018:Tissue Distribution; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D005169:Factor VIII