Pharmacokinetic properties of a pasteurised fibrinogen concentrate

Abstract

The main pharmacokinetic characteristics of a plasma-derived, pasteurised fibrinogen concentrate were assessed in an open, multicentre, non-controlled study in five patients with congenital afibrinogenaemia or severe congenital hypofibrinogenaemia. Plasma samples were assayed for fibrinogen content in laboratories of the participating clinical centres (CCs) and additionally in a central laboratory at Aventis Behring (ABL). The values of the pharmacokinetic variables, using the fibrinogen determination at ABL, yielded a somewhat shorter terminal half-life compared with that determined at the CCs, with median (range) values of 2.7 days (2.5-3.7 days) versus 3.6 days (3.0-5.3 days), respectively. Fibrinogen clearance rate was clearly lower at the ABL with values of 0.91 ml/h/kg (0.84-1.22 ml/h/kg) compared with 1.65 ml/h/kg (0.82-2.55 ml/h/kg) at the CCs. The distribution volume at steady state (V-ss) of 89 ml/kg (81-116 ml/kg) was also smaller at the ABL than at the CCs (101 ml/kg [84-139 ml/kg]). Response, in vivo recovery and area under the curve did not differ noticeably between the laboratories. The normalisation or near normalisation of pre-infusion pathological coagulation tests indicated a good haemostatic efficacy of the tested fibrinogen concentrate, which was also generally well tolerated and not associated with any serious adverse reactions.