“
“Summary.  The pharmacokinetic (PK) response to factor VIII (FVIII) and factor IX varies between Cobimetinib mouse 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 patient’s 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 selleck chemicals 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. The haemostatic efficacy of coagulation factors is closely related to their concentration in the blood. It is common clinical practice to measure factor levels to evaluate and adjust dosing. The plasma level of a coagulation MCE factor is determined by the dose(s) and time(s) of infusion and the patient’s pharmacokinetic (PK) response to the dosing. As in most fields of medical treatment, variation in response between patients is a crucial issue. For example, the half-life of plasma-derived or full-length recombinant factor VIII ranged between 6 and 25 h in two recent, large studies on paediatric and adult patients [1,2]. Thus, a correspondingly wide difference in the factor level between patients is to be expected even after infusion of equivalent doses kg−1 (Fig. 1). Despite this, factor VIII (FVIII) is usually prescribed based on the assumption of an average in vivo recovery of 2 (IU dL−1) (IU kg−1)−1 and half-life of approximately 12 h. The role of PK for more individualized dosing in clinical practice has been discussed previously [1–13]. This review aims to summarize our understanding of the influence an individual patient’s PK on their response to prophylactic treatment. The insight into the influence of PK on dosing should be of value regardless of whether actual PK measurements can be performed at a treatment centre.