A commentary on the differences in pharmacokinetics between recombinant and plasma-derived factor IX and their implications for dosing


Sven Björkman, Department of Pharmaceutical Biosciences, Uppsala University, Box 591, S-751 24 Uppsala, Sweden.
Tel.: +46 18 471 4848; fax: +46 18 471 4003;
e-mail: sven.bjorkman@farmbio.uu.se


Summary.  This commentary aims to summarize all aspects of the difference in pharmacokinetics (PK) between recombinant factor IX (rFIX) and plasma-derived factor IX (pdFIX) and their implications for dosing. PK data were compiled from 17 published studies. The average clearance (CL) of rFIX normally ranged between 7.5 and 9.1 mL h−1 kg−1, whereas that of pdFIX was 3.8–5.4 mL h−1 kg−1. The average terminal half-life was 18–24 h among all 72-h studies on rFIX, in contrast to (normally) 29–43 h for pdFIX. In vivo recovery was more variable. Judging from the pooled data, the typical recovery of rFIX is around two-third that of pdFIX. The difference in PK between rFIX and pdFIX is thus clear-cut and has implications for dosing. As estimated from the compiled data, the dose required to reach any peak level of FIX immediately after administration would be 1.5 times higher for rFIX than for pdFIX, most probably with considerable individual variation. Calculated doses for a patient on a twice weekly prophylactic treatment to achieve a predetermined trough FIX level depended markedly on CL and were about twice as high with rFIX as with pdFIX. In summary, conversion factors between rFIX and pdFIX of 1.5 for single doses and 2 for prophylactic dosing can tentatively be applied; however, the interindividual variance both in recovery and CL of rFIX and pdFIX and the unknown variance in ratios between these PK parameters call for careful monitoring if a switch of treatment is made.