In vivo recovery of factor VIII and factor IX: intra- and interindividual variance in a clinical setting.
In vivo recovery (IVR) is traditionally used as a parameter to characterize the pharmacokinetic properties of coagulation factors. It has also been suggested that dosing of factor VIII (FVIII) and factor IX (FIX) can be adjusted according to the need of the individual patient, based on an individually determined IVR value. This approach, however, requires that the individual IVR value is more reliably representative for the patient than the mean value in the population, i.e. that there is less variance within than between the individuals. The aim of this investigation was to compare intra- and interindividual variance in IVR (as U dL1 per U kg1) for FVIII and plasma-derived FIX in a cohort of non-bleeding patients with haemophilia. The data were collected retrospectively from six clinical studies, yielding 297 IVR determinations in 50 patients with haemophilia A and 93 determinations in 13 patients with haemophilia B. For FVIII, the mean variance within patients exceeded the between-patient variance. Thus, an individually determined IVR value is apparently no more informative than an average, or population, value for the dosing of FVIII. There was no apparent relationship between IVR and age of the patient (1.5-67 years). For FIX, the mean variance within patients was lower than the between-patient variance, and there was a significant positive relationship between IVR and age (13-69 years). From these data, it seems probable that using an individual IVR confers little advantage in comparison to using an age-specific population mean value. Dose tailoring of coagulation factor treatment has been applied successfully after determination of the entire single-dose curve of FVIII:C or FIX:C in the patient and calculation of the relevant pharmacokinetic parameters. However, the findings presented here do not support the assumption that dosing of FVIII or FIX can be individualized on the basis of a clinically determined IVR value.
Björkman
S
S
Hospital Pharmacy, Malmö University Hospital, Malmö, Sweden. sven.bjorkman@farmbio.uu.se
Folkesson
A
A
Berntorp
E
E
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005164:Factor IX / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005169:Factor VIII / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007223:Infant; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
D005169:Factor VIII; D005164:Factor IX