Pharmacokinetics and dose requirements of factor VIII over the age range 3–74 years

Björkman, Sven; Folkesson, Anna; Jönsson, Siv

doi:10.1007/s00228-009-0676-x

Cited by 137 publications

(39 citation statements)

References 34 publications

(69 reference statements)

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“…The final two-compartment model with an additive residual error model, age, as a covariate for CL, and V ss similar to the expected plasma volume of the patient, was found to fit the data for both younger and older patients. This finding is in accord with PK modeling data based on other large databases for FVIII treatment 37,39,41,42. The FVIII levels predicted by the model were in close agreement with observed levels of FVIII in patients.…”

Section: Pk-guided Prophylaxissupporting

confidence: 89%

Advancing personalized care in hemophilia A: ten years’ experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method

Berntorp¹,

Spotts²,

Patrone³

et al. 2014

BTT

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Detailed analysis of data from studies of recombinant antihemophilic factor produced using a plasma/albumin-free method (rAHF-PFM) in previously treated patients showed a substantial level of interpatient variation in pharmacokinetics (PKs), factor VIII dosing, and annualized bleed rate (ABR), suggesting that individual patient characteristics contributed to outcome. For example, plasma half-life (t1/2), recovery, and clearance appeared to differ between patients aged <6 years and 10–65 years. Prophylaxis resulted in lower ABRs than episodic treatment in both age groups; better adherence to the prophylactic regimen resulted in a lower ABR in patients aged 10–65 years. The weekly frequency of dosing and adherence to dosing were both significantly and inversely related to the rate of bleeding (young children, P<0.0001 for both all bleeds and joint bleeds; older patients, P<0.0001 for all bleeds and P<0.05 for joint bleeds), as was adherence to dosing frequency (P<0.0001 for all comparisons). A post-marketing randomized study of prophylaxis demonstrated that a PK-guided dosing regimen, based on an individual patient’s rAHF-PFM PK (infusion interval, estimated t1/2, and recovery), was as effective as standard prophylaxis and that both prophylactic regimens were superior to episodic treatment with respect to ABR and quality of life measures. Thus, compared with standard prophylaxis, the PK-guided regimen achieved comparable efficacy with fewer weekly infusions. A two-compartment population PK model describes the PK data across the entire age range and forms the basis for future PK-guided therapy with rAHF-PFM. The model confirmed a shorter t1/2 and faster clearance of rAHF-PFM in children <6 years of age versus patients ≥10 years and predicted similar PK parameters with either a full or reduced blood sampling schedule, offering the potential for the use of PK-guided, individualized treatment in the routine clinical care setting.

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Section: Pk-guided Prophylaxissupporting

confidence: 89%

Advancing personalized care in hemophilia A: ten years’ experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method

Berntorp¹,

Spotts²,

Patrone³

et al. 2014

BTT

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“…In a study of factor VIII (FVIII), 34 patients (aged 7–74 years), including 16 children, were used for model building [86]. Body weight and age were found to be significant covariates.…”

Section: Resultsmentioning

confidence: 99%

Pediatric Dosing and Body Size in Biotherapeutics

Shi

Derendorf

2010

Pharmaceutics

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Although pediatric doses for biotherapeutics are often based on patients' body weight (mg/kg) or body surface area (mg/m2), linear body size dose adjustment is highly empirical. Growth and maturity are also important factors that affect the absorption, distribution, metabolism and excretion (ADME) of biologics in pediatrics. The complexity of the factors involved in pediatric pharmacokinetics lends to the reconsideration of body size based dose adjustment. A proper dosing adjustment for pediatrics should also provide less intersubject variability in the pharmacokinetics and/or pharmacodynamics of the product compared with no dose adjustment. Biological proteins and peptides generally share the same pharmacokinetic principle with small molecules, but the underlying mechanism can be very different. Here, pediatric and adult pharmacokinetic parameters are compared and summarized for selected biotherapeutics. The effect of body size on the pediatric pharmacokinetics for these biological products is discussed in the current review.

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“…In the frame of this favorable scenario, the optimal form of replacement therapy is long-term regular prophylaxis since childhood, which is able to overthrow bleeding frequency particularly into joints, therefore reducing the development of chronic arthropathy [5,6]. Patients with hemophilia A on prophylaxis require intravenous injections every other day or three times per week, while those with hemophilia B are usually treated twice weekly, owing to the longer half-life of FIX over FVIII (18–20 h instead of 10–12 h) [7,8]. In this light, the development of a new generation of coagulation factors endowed with extended half-life may overall improve the management of PWH and their quality of life by reducing the burden of frequent intravenous injections, the need for central venous lines in children and the loss of adherence to treatment typically seen in adolescents.…”

Section: Introductionmentioning

confidence: 99%

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

Mancuso

Santagostino

2017

JCM

110

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The development of a new generation of coagulation factors with improved pharmacokinetic profile will change the paradigm of treatment of persons with hemophilia (PWH). The standard treatment in PWH is represented by regular long-term prophylaxis that, given intravenously twice or thrice weekly, is associated with a not-negligible burden on patients’ quality of life. The availability of drugs with improved pharmacokinetic profile may improve prophylaxis feasibility and protection against bleeding episodes. This article summarizes the main results obtained from clinical trials with modified factor VIII (FVIII) and factor IX (FIX) molecules. Published literature on new molecules for replacement treatment in hemophilia A and B was retrieved using PubMed search, and all ongoing clinical trials have been researched via . Such new molecules are usually engineered to have a longer plasma half-life than that which has been obtained by chemical modification (i.e., conjugation with polyethylene glycol, PEG) or by creating recombinant fusion proteins. Results from phase I/III studies in previously treated adults and children are now available for the vast majority of new products, including the results of their use in a surgical setting. On the contrary, trials involving previously untreated patients are still ongoing for all and results not yet available.

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Pharmacokinetics and dose requirements of factor VIII over the age range 3–74 years

Abstract: dose requirements of factor VIII over the age range 3-74 years.

Cited by 137 publications

References 34 publications

Advancing personalized care in hemophilia A: ten years’ experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method

Advancing personalized care in hemophilia A: ten years’ experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method

Pediatric Dosing and Body Size in Biotherapeutics

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

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Pharmacokinetics and dose requirements of factor VIII over the age range 3–74 years

Abstract: dose requirements of factor VIII over the age range 3-74 years.

Cited by 137 publications

References 34 publications

Advancing personalized care in hemophilia A: ten years&rsquo; experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method

Advancing personalized care in hemophilia A: ten years&rsquo; experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method

Pediatric Dosing and Body Size in Biotherapeutics

Outcome of Clinical Trials with New Extended Half-Life FVIII/IX Concentrates

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Product

Resources

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Advancing personalized care in hemophilia A: ten years’ experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method

Advancing personalized care in hemophilia A: ten years’ experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method