5 years ago

In silico evaluation of limited blood sampling strategies for individualized recombinant factor IX prophylaxis in hemophilia B patients

F. W. G. Leebeek, M. H. Cnossen, H. C. A. M. Hazendonk, K. Fijnvandraat, T. Preijers, R. A. A. Mathôt
Essentials Individual pharmacokinetic (PK) parameters can be obtained by limited sampling strategies (LSSs). Following 100 IU kg−1 rFIX, LSSs with 1 to 3 samples were evaluated in 5000 simulated subjects. For all LSSs, estimated individual PK parameters showed acceptable bias and precision. One sample between 10 min–3 h and two between 48 h–56 h showed best predictive performance. Summary Background Patients with severe hemophilia B regularly administer prophylactic intravenous doses of clotting factor IX concentrate to maintain a trough level of at least 0.01 IU mL−1 in order to prevent joint bleeds. Assessment of individual pharmacokinetic (PK) parameters allows individualization of the recombinant factor IX (rFIX) dose. Aim To evaluate the predictive performance of limited sampling strategies (LSSs) with one to three samples to estimate individual PK parameters of rFIX. Methods Monte Carlo simulations were performed to obtain 5000 concentration–time profiles by the use of population PK parameters for rFIX from literature. Eleven LSSs were developed with one, two or three samples taken within an 80-h interval following administration of 100 IU kg−1 rFIX. Clearance (CL), half-life (t1/2), time to 1% and steady-state distribution volume (Vss) were estimated for each simulated individual by the use of Bayesian analysis. Results For each LSS, average bias was small for CL (range − 1.5% to 1.4%), t1/2 (range − 4.5% to − 0.7%), time to 1% (range − 2.9% to 0%), and Vss (range − 3.7% to 0.3%). Imprecision for these parameters ranged from 6.4% to 11.9%, from 10.3% to 15.6%, from 7.3% to 10.9%, and from 9% to 20.1%, respectively. The best predictive performance was achieved with one sample taken between 10 min and 3 h and two samples taken between 48 h and 56 h after administration of rFIX. Conclusions This study demonstrates that limited sampling strategies, used for individualized dosing of rFIX in hemophilia B patients, can be developed and evaluated by in silico simulation.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jth.13771

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.