title: Prophylaxis in factor IX deficiency product and patient variation.
abstract: To determine the dosing needed to maintain a prophylactic level of factor IX (FIX) >/=2%, 15 non-inhibitor severe (</=1% FIX) deficient subjects participated in a double-blind, two-period crossover study to assess the pharmacokinetics of two FIX concentrates, Mononine (pd-FIX), an ultra-high-purity plasma-derived concentrate, and BeneFix (r-FIX), a recombinant product. The median recovery in the pd-FIX group was 1.67 IU dL(-1) per IU kg-1+/-1.07 vs. 0.86 IU dL(-1) per IU kg(-1)+/-0.32 in the r-FIX group (P = 0.0002). The median half-life for pd-FIX was 12.9 +/-1.7 h compared with 13.7 +/- 2.9 h for r-FIX (P = 0.016). Fitted dose activity curves were computer-simulated to depict multiple-dose activity curves for each patient with each product that would maintain prophylactic levels of >/=2%. Based on pharmacokinetic analysis the median amount of concentrate needed to maintain a prophylactic level >/=2% for 30 days when administered every third day is 677 IU kg(-1) pd-FIX (range 388-6005 IU kg(-1) pd-FIX) compared with 1168 IU kg(-1) r-FIX (range 268-13085 IU kg(-1) r-FIX). The median cost for 30 days of prophylaxis of an average 25-kg 8-year-old child at the current University of Iowa Price (0.87 US dollars Mononine/0.86 US dollars BeneFix as of December 2002) if given every third day would be 19,972 US dollars and 34,456 US dollars for r-FIX. However, because of wide inter-patient variability in recovery and half-life, pharmacokinetic evaluation of each patient is necessary to determine the appropriate dosing schedule and product best suited for prophylaxis.
authors.affiliation: University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. c-kisker@uiowa.edu
authors.forename: C T
authors.initials: CT
authors.lastname: Kisker
authors.forename: A
authors.initials: A
authors.lastname: Eisberg
authors.forename: B
authors.initials: B
authors.lastname: Schwartz
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003362:Cost-Benefit Analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D016527:Drug Costs; D005164:Factor IX / Q000008:administration & dosage* / Q000191:economics / Q000493:pharmacokinetics; D006207:Half-Life; D006395:Hemarthrosis / Q000209:etiology / Q000517:prevention & control; D002836:Hemophilia B / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000191:economics / Q000493:pharmacokinetics
chemical_list: D011994:Recombinant Proteins; C093388:Mononine; D005164:Factor IX