title: Pharmacokinetics of Beriplex P/N prothrombin complex concentrate in healthy volunteers.
abstract: Prothrombin complex concentrates (PCCs) are widely administered for emergency oral anticoagulation reversal and for coagulation defects in liver disease. Pharmacokinetic data may help to optimize treatment. The objective of this study was to characterize the pharmacokinetics of a PCC (Beriplex P/N) containing coagulation factors II (FII), VII (FVII), IX (FIX) and X (FX) and anticoagulant proteins C and S. Fifteen healthy volunteers received a single rapid 50 IU/kg infusion of PCC and underwent frequent blood sampling until 144 hours (h) after infusion. Coagulation factors and anticoagulant protein pharmacokinetic parameters were estimated by non-linear regression. The mean infusion rate of PCC was 7.9 ml/min, equivalent to 196.4 IU/min. By the earliest post-infusion sampling point at 5 minutes (min), plasma FIX concentration increased by a median of 73%. Median increases in FII, FVII and FX at 5 min were 122%, 62% and 158%, respectively. Proteins C and S also increased rapidly. The median terminal half-life of FIX was 16.7 h, FII 59.7 h, FVII 4.2 h and FX 30.7 h. The median in-vivo recovery of FIX was 1.57 %/IU/kg and that of the other three coagulation factors > 2 %/IU/kg. Plasma concentration of thrombogenicity marker D-dimer did not increase, and there was no clinical evidence of thrombosis. Through up to 12 weeks follow-up there were no laboratory findings indicating PCC-related viral exposure. Rapid PCC infusion produced prompt sustained increases in coagulation factors and anticoagulant proteins with no clinical evidence of thrombosis or viral transmission.
authors.affiliation: University Hospital Munich - Grosshadern, Medical Clinic III, Department of Haematology and Oncology, Ludwig Maximilian University, Munich, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Ostermann
authors.forename: Sabine
authors.initials: S
authors.lastname: Haertel
authors.forename: Sigurd
authors.initials: S
authors.lastname: Knaub
authors.forename: Uwe
authors.initials: U
authors.lastname: Kalina
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jung
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000493:pharmacokinetics*; D001779:Blood Coagulation Factors / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005164:Factor IX / Q000493:pharmacokinetics*; D005167:Factor VII / Q000493:pharmacokinetics*; D005170:Factor X / Q000493:pharmacokinetics*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry; D006801:Humans; D008107:Liver Diseases / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011516:Prothrombin / Q000096:biosynthesis* / Q000493:pharmacokinetics; D012044:Regression Analysis; D013927:Thrombosis; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D004338:Drug Combinations; D005338:Fibrin Fibrinogen Degradation Products; C525441:factor IX, factor VII, factor X, prothrombin drug combination; C036309:fibrin fragment D; D005167:Factor VII; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X