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Pharmacokinetics of recombinant factor VIII (Kogenate‐FS ® ) in children and causes of inter‐patient pharmacokinetic variability

2006; Wiley; Volume: 12; Issue: s4 Linguagem: Inglês

10.1111/j.1365-2516.2006.01333.x

1365-2516

Chris Barnes, David Lillicrap, Janneth Pazmino‐Canizares, Victor S. Blanchette, A. M. Stain, Dewi Clark, Caroline Hensmen, Manuel Carção,

Platelet Disorders and Treatments

Summary. Understanding the pharmacokinetics (PK) of factor VIII (FVIII) is important in the management of patients with haemophilia A. We studied the PK of FVIII in order to determine aetiological factors contributing to PK variability of FVIII in children. Twenty children with haemophilia A (mean age 12.8 years) were administered a single bolus of 50 U kg −1 of recombinant FVIII (rFVIII; Kogenate‐FS ® , Bayer). The mean incremental FVIII recovery was 1.87 (U mL −1 )/(U kg −1 ) (range: 1.25–2.76) and the mean FVIII half‐life was 10.7 h (range: 7.8–15.3). FVIII recovery was positively correlated with body surface area (BSA; P = 0.04). FVIII half‐life was positively correlated with preinfusion levels of von Willebrand factor antigen (VWF:Ag) ( P = 0.0001) and was reduced in patients ( n = 6) with very low FVIII inhibitor titres (<0.5 BU) vs. those ( n = 14) with negative inhibitor titres ( P = 0.06). These observations suggest that (i) young children with haemophilia in comparison with adults have a low recovery of FVIII and that this might be explained by differences in body composition (BSA, plasma volume), (ii) levels of VWF:Ag may explain some of the differences in the half‐life and clearance of FVIII and (iii) very low inhibitor titres, previously regarded as clinically insignificant, may actually be significant and should be evaluated in the context of PK studies.