Pharmacokinetics, thrombogenicity and safety of a double-treated prothrombin complex concentrate

The pharmacokinetic profile, the thrombogenicity and the virus safety of Preconativ, a PCC subjected both to virus removal procedure and dry-heat treatment were studied. Preconativ is produced from plasma pool, negative both for HBsAg and for antibodies to HIV. To further reduce the risk of virus transmission, the manufacturing process includes hydrophobic gel chromatography and dry-heat treatment at +68 degrees C for 48 hours. Nine patients with hemophilia B participated in a single dose, pharmacokinetic study. The decay curves of factor IX clotting activity were evaluated by model-independent methods. The Clearance and the Mean Residence Time were very similar to those previously reported for untreated PCC. The Volume of Distribution Area and In Vivo Recovery resulted inversely correlated and respectively larger and smaller than those of untreated PCC. A slight fall in platelet count and Antithrombin III level and an increase of Beta-Thromboglobulin and Fibrinopeptide A concentration were found, indicating a clear-cut activation of the coagulation process during the first hours following Preconativ administration. Seven patients (2 of the ones enrolled in the pharmacokinetic study) were completely fulfilling the SSC-ISTH criteria for virus safety prospective study. The follow up of these patients did not show any transaminases elevation or seroconversion against HBV, HCV or HIV. These findings did not change over a 3-5 year follow up in 3 out of 7 patients, repeatedly infused with Preconativ.