#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Pharmacokinetics in haemophilia treatment


Authors: J. Máchal
Authors‘ workplace: Oddělení dětské hematologie FN Brno a LF MU Brno
Published in: Transfuze Hematol. dnes,25, 2019, No. 3, p. 230-240.
Category: Review/Educational Papers

Overview

Haemophilia is an inborn X-linked bleeding disorder, which is caused by a deficiency of coagulation factor VIII in haemophilia A and factor IX in haemophilia B. Currently, the standard treatment regimen for severe forms of the disease is the prophylactic intravenous administration of the deficient factor. The initial dosage is assessed identically for all persons with haemophilia and subsequently modified empirically depending on the individual bleeding phenotype. Due to the large inter-individual variability in the response, to the administered factor, this „one-size-fits-all “approach is now deemed obsolete. Treatment individualization and personalization is gaining in importance. One of the most important ways to individualize treatment is using a pharmacokinetic approach. Pharmacokinetics of the administered concentrate provide to detailed and individually specific information regarding treatment efficacy. Based on pharmacokinetics, it is possible to adjust treatment – dose, frequency of infusions and even the choice of factor concentrate. It is complicated to perform a classic pharmacokinetic assessment, which is why a population pharmacokinetic approach is becoming more and more attractive. Using sophisticated population models, it is possible to assess the individual pharmacokinetics from the limited number of samples obtained in different situations. Population pharmacokinetic models are easily available for clinicians as internet-based applications. Apart from assessing the individual pharmacokinetics, they can be used to evaluate the efficacy of the current dosing regimen and generate a new one based on the required frequency of application, trough level or dose. Mobile applications, which will allow each patient to gain access, to his/her current factor level are being developed. With this knowledge, a haemophiliac will be able to assess the suitability of a planned activity at any given moment and schedule their activities in advance according to the estimated protection level.

Keywords:

haemophilia – individualization – pharmacokinetics – population pharmacokinetics


Sources

1. Mannucci PM, Tuddenham EG. The hemophilias – from royal genes to gene therapy. N Engl J Med 2001;344(23):1773–1779.

2. Berntorp E, Shapiro AD. Modern haemophilia care. Lancet 2012;379(9824):1447–1456.

3. Fischer K, Ljung R. Primary prophylaxis in haemophilia care: guideline update 2016. Blood Cells Mol Dis 2017;67:81–85.

4. Ahlberg A. Haemophilia in Sweden VII. incidence, treatment and prophylaxis of arthropathy and other musculo-skeletal manifestations of haemophilia A and B. Acta Orthop Scand 1965:77:3–132.

5. Manco-Johnson MJ, Abshire TC, Shapiro AD, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007;357(6):535–544.

6. Skinner MW. WFH: closing the global gap – achieving optimal care. Haemophilia 2012; 4: 1–12.

7. den Uijl IE, Fischer K, Van Der Bom JG, et al. Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity levels. Haemophilia 2011;17(1):41–44.

8. Iorio A, Edginton A, Blanchette V, et al. Performing and interpreting individual pharmacokinetic profiles in patients with hemophilia A or B: rationale and general considerations. Res Pract Thromb Haemost 2018;2(3):535–548.

9. Carcao MD, Iorio A. Individualizing factor replacement therapy in severe hemophilia. Semin Thromb Hemost 2015;41(8):864–871.

10. Ljung R, Fischer K, Carcao M, et al. Practical considerations in choosing a factor VIII prophylaxis regimen: role of clinical phenotype and trough levels. Thromb Haemost 2016;115(5):913–920.

11. Fijnvandraat K, Peters M, ten Cate JW. Inter-individual variation in half-life of infused recombinant factor VIII is related to pre-infusion von Willebrand factor antigen levels. Br J Haematol 1995;91(2):474–476.

12. Björkman S, Carlsson M. The pharmacokinetics of factor VIII and factor IX: methodology, pitfalls and applications. Haemophilia 1997;3(1):1–8.

13. Collins PW, Fischer K, Morfini M, et al. Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia. Haemophilia 2011;17(1):2–10.

14. Björkman S, Folkesson A, Jönsson S. Pharmacokinetics and dose requirements of factor VIII over the age range 3–74 years: a population analysis based on 50 patients with long-term prophylactic treatment for haemophilia A. Eur J Clin Pharmacol 2009;65(10):989–998.

15. Björkman S, Oh M, Spotts G, et al. Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight. Blood 2012;119(2):612–618.

16. Iorio A, Blanchette V, Blatny J, et al. Estimating and interpreting the pharmacokinetic profiles of individual patients with hemophilia A or B using a population pharmacokinetic approach: communication from the SSC of the ISTH. J Thromb Haemost 2017;15(12):2461–2465.

17. Ar MC, Baslar Z, Soysal T. Personalized prophylaxis in people with hemophilia A: challenges and achievements. Expert Rev Hematol 2016;9(12):1203–1208.

18. Blatný J, Zapletal O, Köhlerová S, et al. Farmakokinetika jako nástroj k optimalizaci léčby osob s hemofilií. Transfuze Hematol dnes 2014;20(4):103–106.

19. Iorio A. Using pharmacokinetics to individualize hemophilia therapy. 2017;1:595–604.

20. Pasca S, Milan M, Sarolo L, et al. PK-driven prophylaxis versus standard prophylaxis: when a tailored treatment may be a real and achievable cost-saving approach in children with severe hemophilia A. Thromb Res 2017;157:58–63.

21. Peyvandi F, Garagiola I, Seregni S. Future of coagulation factor replacement therapy. J Thromb Haemost 2013;11(1):84–98.

22. Gringeri A, Wolfsegger M, Steinitz KN, et al. Recombinant full-length factor VIII (FVIII) and extended half-life FVIII products in prophylaxis – new insight provided by pharmacokinetic modelling. Haemophilia 2015;21(3):300–306.

23. Lee M, Morfini M, Schulman S, et al. The design and analysis of pharmacokinetic studies of coagulation factors – International society on thrombosis and haemostasis, inc. Dostupné na www: www.isth.org/members/group_content_view.asp?group=100348&id=159244.

24. Garraffo R, Iliadis A, Cano JP, et al. Application of Bayesian estima-tion for the prediction of an appropriate dosage regimen of amikacin. J Pharm Sci 1989;78(9):753–757.

25. Hazendonk HCAM, van Moort I, Mathôt RAA, et al. Setting the stage for individualized therapy in hemophilia: what role can pharmacokinetics play?” Blood Rev 2018;32(4):265–271.

26. Jankovičová D, Šteňo D, Prigancová T, et al. Manažment veľkých operácií u pacientov s hemofíliou A kontinuálnou infúziou a bolusovými injekciami FVIII – farmakokinetický prístup k liečbe. Transfuze Hematol dnes 2017;23(2):61–72.

27. Morongová A., Jankovičová D, Bátorová A, et al. Analýza zhody vyšetrenia inhibítorov FVIII Bethesda metódou a modifikovanou Nijmegen metódou a vplyv hraničných titrov inhibítorov na farmakodynamiku a farmakokinetiku FVIII u pacientov s hemofíliou A. Transfuze Hematol dnes 2016;22(3):172–181.

27. Iorio A, Fischer K, Blanchette V, et al. Tailoring treatment of haemophilia B: accounting for the distribution and clearance of standard and extended half-life FIX concentrates. Thromb Haemost 2017;117(6):1023–1030.

28. Lock J, de Bekker-Grob EW, Urhan G, et al. Facilitating the implementation of pharmacokinetic-guided dosing of prophylaxis in haemophilia care by discrete choice experiment. Haemophilia 2016;22(1):1–10.

29. McEneny-King A, Iorio A, Foster G, et al. The use of pharmacokinetics in dose individualization of factor VIII in the treatment of hemophilia A. Expert Opin Drug Metab Toxicol 2016;12(11):1313–1321.

Labels
Haematology Internal medicine Clinical oncology
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#