Kinetic evaluation of four Factor VIII concentrates by model‐independent methods

Abstract

Single‐dose kinetics of 4 Factor VIII concentrates (Kryobulin, Hemofil T, Koate, cryoprecipitate) were studied in 41 patients with haemophilia‐A. Model‐independent methods were adopted for calculating the kinetic parameters (area under the curve, clearance, area under the moment curve, mean residence time, volume of distribution at steady‐state). No substantial difference was observed in the kinetic characteristics of the 4 Factor VIII concentrates. A considerable interindividual variability of the calculated kinetic parameters was demonstrated for all concentrates. Our findings support the need to individualize Factor VIII dosage.

Pharmacokinetics and dose requirements of factor VIII over the age range 3–74 years

“…The mean CL of 222 mL/h in a 24-year-old, 68-kg subject equals 3.26 mL/h per kg, which is similar to the accepted mean value of 3 mL/h per kg in an "adult" patient, and the elimination t1/2 estimates (Fig. 3b) for "adults" are scattered around the normal mean value of 12-14 h. The findings of a decreased CL per kg BW and an increased t1/2 with age are also in general agreement with previous studies [2,7,10,14]. The mean estimate of BL was rather high however, given that only 3 of the 50 patients were diagnosed with moderate haemophilia, and the IIV had a relative CV of 110%.…”

“…Weight-adjusted clearance (CL) of FVIII (i.e. in millilitres per hour per kilogram) has generally been found to decrease with age and/or body weight (BW) during growth from infancy to adulthood, with a corresponding increase in terminal half-life (t1/2) [2,7,10,14]. Relationships of CL and t1/2 with plasma level of von Willebrand factor have been reported [8][9][10][11] but also refuted [12].…”

“…Relationships of FVIII PK with patient characteristics have been investigated in several studies [2,[6][7][8][9][10][11][12][13][14] on limited numbers of patients. Weight-adjusted clearance (CL) of FVIII (i.e.…”

Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia

“…At a later time, all samples of the entire decay curve must be assayed simultaneously, against the same calibration curve, to reduce the error of FVIII/IX assay. A model-independent method should be preferred to avoid the problems of best fitting of compartment methods, more likely to be affected by errors of best fitting [14,50,51]. Less demanding half-life assessment based on a reduced, but well-defined, number of sampling points may provide good results, with limited loss of information [52,53].…”

“…The best documented example is that BWadjusted clearance (CL) of FVIII (i.e. in mL h )1 kg )1 ) has been found to decrease with age and/or BW during growth from infancy to adulthood, with a corresponding increase in terminal half-life [1,2,7,[14][15][16]. However, these correlations are too weak to be used to predict reliably FVIII PK in individual patients [1,2].…”