Clinical Trials of Recombinant Factor VIII

WhiteII, Gilbert C.; McMillan, Campbell W.; Gomperts, Edward D.; AddiegoJr., Joseph E.; Brackmann, H.‐H.; Brettler, Doreen B.; Gill, Joan Cox; Goldsmith, Jonathon C.; Hoots, W. Keith; Kessler, Craig M.; Kisker, C. Thomas; Laurian, Y.; Lewis, Bryan; Lusher, Jeanne M.; Mannucci, P. M.; Morfini, M; Scharrer, I.; Schulman, Sam; Lee, Martin L.; Courter, S; Kingdon, Henry S.; Roberts, Harold R.

doi:10.1007/978-1-4615-3698-7_17

Cited by 6 publications

(10 citation statements)

References 28 publications

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“…As re-calculated from [9] the average doses of rFIX would be about 3800 IU every third day and 1250 IU alternate days -an approximately threefold difference over all. In fair agreement with these separate estimations, the two cross-over studies [37,38] demonstrated that FIX plasma levels 48 h after a dose of rFIX were only approximately 50-70% of those obtained with the same dose of pdFIX. This can be directly translated to a 1.5-to 2-fold increase in dose requirement during prophylactic treatment.…”

Section: Pharmacokinetic Implications Of Dosingsupporting

confidence: 60%

“…Comparisons between the methodologically most robust studies on either species indicate that the average CL of recombinant FIX is twice as high as that of pdFIX [10]. This difference is confirmed in cross-over comparisons [37,38] [5,10,36]. The difference in CL between rFIX and pdFIX appears to be greater and more consistent between studies, than the difference in half-life, which demonstrate that the comparison cannot be based on only a single PK parameter.…”

Section: Pharmacokinetic Implications Of Dosingmentioning

confidence: 92%

“…Data for rFIX are available, however, for the entire age range of patients with haemophilia B [9,[37][38][39][40][41]43]. There was no relationship between age and terminal half-life.…”

Section: Implications For Adults Compared To Childrenmentioning

confidence: 99%

“…The observed difference in IVR of recombinant vs. pdFIX [37,38,43] needs to be considered when prescribing this concentrate as it affects the obtained peak level in the treatment of a bleed or for covering surgery.…”

Section: In Vivo Recovery (Ivr)mentioning

confidence: 99%

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Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia

Fischer²,

et al. 2010

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Summary. The pharmacokinetic (PK) response to factor VIII (FVIII) and factor IX varies between patients and this has important clinical implications for treatment. Although PK is affected by patient characteristics, this relationship is too weak to infer a result for an individual and, if required, PK must be measured. An important determinant of the efficacy of prophylaxis is the length of time an individual spends with a low level of coagulation factor. This time is more dependent on the patientÕs coagulation factor half-life and the frequency of dosing than in vivo recovery and dose infused. Improved understanding of the effect of PK and dose frequency on factor levels in patients on prophylaxis will help tailor regimens to individuals better and allow more cost effective use of coagulation factor concentrates. Calculations suggest that adults need less FVIII per kg body weight than children. The effect of half-life on trough levels questions the logic of Monday, Wednesday, Friday dosing and suggests a role for innovative regimens including low-dose daily treatment which leads to either higher trough levels or decreased FVIII requirement. This may expand access to prophylaxis in healthcare systems with limited resources and potentially improve patient outcomes. The ideal trough level will vary between individuals and at different times of their lives and may be <1 IU dL )1. If PK is to be used in routine clinical practice, a simplified method for its measurement is required and this methodology is becoming available.

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Section: Pharmacokinetic Implications Of Dosingsupporting

confidence: 60%

Section: Pharmacokinetic Implications Of Dosingmentioning

confidence: 92%

“…Data for rFIX are available, however, for the entire age range of patients with haemophilia B [9,[37][38][39][40][41]43]. There was no relationship between age and terminal half-life.…”

Section: Implications For Adults Compared To Childrenmentioning

confidence: 99%

Section: In Vivo Recovery (Ivr)mentioning

confidence: 99%

See 2 more Smart Citations

Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia

Fischer²,

et al. 2010

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show abstract

“…No human or animal protein is used during the purification steps of recombinant FIX nor is any added to the final product for formulation. Pharmacokinetic and efficacy studies in previously treated patients gave satisfactory results, 18 even though the in vivo recovery is substantially lower than that of plasma-derived factor, probably because of minor differences in the structure of the recombinant protein.…”

Section: Recombinant Factorsmentioning

confidence: 97%