In another study [61], nine patients with VWD type 3, six with type 2B, one with type 2A, and one patient with

type 1/2N were infused with one dose of approximately 50 or 100 IU ristocetin cofactor activity (RCoF) per kg of VWF (Human), a product with a very low content of FVIII. The FVIII:C rate of synthesis was found to be 6.4 U dL−1 h−1 (range: 4.4–8.8). A more recent study by Kessler et al. [62] investigated the pharmacokinetic diversity of two VWF/FVIII concentrates (a new, high purity, human plasma-derived (pd)VWF/FVIII concentrate, Wilate and an intermediate-purity selleck compound (pd)VWF/FVIII concentrate, Humate-P) in patients with congenital VWD. Wilate showed parallel decay curves for VWF:RCo and FVIII clotting activity (FVIII:C) over time, while FVIII:C of Humate-P

displayed a plateau between 0 and 12–24 h. Bioequivalent pharmacokinetic properties for VWF between Wilate and Humate-P were demonstrated. It is difficult to analyse results in comparative studies when completely different amounts of clotting factor concentrate are given, therefore the plot was simplified according to Cmax. Results showed perfect biphasic Abiraterone purchase decay. The authors concluded that the pharmacokinetic profile of Wilate, combined with the 1:1 VWF/FVIII ratio, should theoretically facilitate dosing and laboratory monitoring of VWF replacement to prevent bleeding in VWD patients. When estimating three pharmacokinetic parameters by model-independent method, clearance (mL h−1 kg−1), i.e. the volume of plasma made free of the drug, is very important. The mean residence time (h)

also needs to be considered, i.e. the rate at which the drug concentration declines after the dose, independently of the shape (monophasic or biphasic) of the decay curve. Finally, the volume of distribution area needs to be measured: it indicates if the entire decay curve is high, normal or low with respect to the dose. It is not affected by the fitting errors of the first part of the curve, as in vivo recovery. Paediatric Carnitine palmitoyltransferase II patients have the same right to well-investigated therapies as adults. There are, however, several reasons why it is more difficult to study a medicinal product in paediatric patients, particularly in very young children. There is a lack of high-quality pharmacokinetic, efficacy and safety data due to ethical issues and because drug regulatory authorities until recently did not request evidence for this patient group. Intraindividual and age-dependent developmental aspects have to be considered with respect to the growing child. Recent pharmacokinetic studies of factor IX (FIX) and FVIII in children have mostly shown differences compared to adults (in vivo recovery is lower, body weight-adjusted clearance is higher and elimination half-life (t1⁄2) is on average shorter), but pharmacokinetics cannot be predicted from age and bodyweight [63].