title: Pharmacokinetics, thrombogenicity and safety of a double viral inactivated factor IX concentrate compared with a prothrombin complex concentrate.
abstract: Therapeutic options for developing countries have to assure an optimum safety and efficacy and low-cost antihaemophilic concentrates. A single blind randomized crossover study was carried out in 12 previously treated HB patients, comparing the pharmacokinetics (PK), thrombogenicity (TG) and safety of two plasma-derived double-inactivated (solvent/detergent heating at 100 degrees C, 30 min) factor IX (FIX) concentrates, UMAN COMPLEX DI (product A) [plasma-derived prothrombin concentrates (PCC)] and a high purity FIX concentrate AIMAFIX DI (product B, HPFIX). In a non-bleeding state, they received one single intravenous dose 50 IU FIX kg(-1) of PCC or HPFIX, and after a wash-out period of 14 days, the other product. We evaluated acute tolerance and determined PK parameters based on FIX levels measured over a 50 h postinfusion period. We studied fibrinogen, platelets, antithrombin, F1 + 2, TAT, D-dimer, over a 360 min postinfusion period. Ten cases remained in on-demand treatment for 6 months, five with PCC and five with HPFIX. PK and anti-FIX inhibitors were repeated at 3 and 6 months. No inhibitors were detected. PK values (PCC vs. HPFIX): clearence (CL; mL h(-1) kg(-1)) 5.2 +/- 1.4 vs. 6.5 +/- 1.4; the volume of distribution at steady state (mL kg(-1)) 154.9 +/- 54.9 vs. 197.5 +/- 72.5; mean residence time (h) 29.7 +/- 8.1 vs. 30.7 +/- 9.2; T(1/2) (h) 22.3 +/- 7 vs. 23.5 +/- 12.3; incremental recovery (IR; U dL(-1) U(-1) kg(-1)) 0.96 +/- 0.17 vs. 0.76 +/- 0.13. HPFIX showed significant lower IR and higher CL. There were no differences in PK at 3 and 6 months. In TG, significant increments in TAT and F1 + 2 at 30 min and 6 h were found with PCC. Product B PK results agrees with reported results for other HPFIX preparations. Use of PCC product A has to consider its thrombogenic activity.
authors.affiliation: Centro Nacional de Hemofilia, Banco Municipal de Sangre del Distrito Capital, Caracas, Venezuela. hnossaez@telcel.net.ve
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Sáez
authors.forename: A
authors.initials: A
authors.lastname: Hong
authors.forename: A
authors.initials: A
authors.lastname: Arguello
authors.forename: M
authors.initials: M
authors.lastname: Echenagucia
authors.forename: A
authors.initials: A
authors.lastname: Boadas
authors.forename: F
authors.initials: F
authors.lastname: Fabbrizzi
authors.forename: F
authors.initials: F
authors.lastname: Minichilli
authors.forename: N B
authors.initials: NB
authors.lastname: Bosch
mesh_terms: D000293:Adolescent; D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D005164:Factor IX / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D002836:Hemophilia B / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000097:blood; D010976:Platelet Count / Q000379:methods; D011516:Prothrombin / Q000032:analysis; D016037:Single-Blind Method
chemical_list: D015415:Biomarkers; D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; C025667:prothrombin complex concentrates; D000990:Antithrombin III; D011516:Prothrombin; D005164:Factor IX; D005340:Fibrinogen; D010447:Peptide Hydrolases