Comparative study of four different pharmacokinetic computer programs: case study of a factor VIII preparation

Planas-Pascual, Bernat; Montoro, Julia

doi:10.1007/s002280050249

Cited by 7 publications

(5 citation statements)

References 6 publications

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“…The complete set of collected data is summarized in Table 1. A total of 60 publications were included representing mice, dogs, and humans with HA as well as normal mice, rats, rabbits, and monkeys 7–11,14–16,25–76. A summary of the NCA derived PK parameters CL, V ss , MRT, and half‐life ( t 1/2 ) are presented in Table 2.…”

Section: Resultsmentioning

confidence: 99%

Allometry of Factor VIII and Informed Scaling of Next-Generation Therapeutic Proteins

Kosloski

Pisal

Mager

et al. 2013

Journal of Pharmaceutical Sciences

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Allometric scaling has been applied to the pharmacokinetics (PK) of factor VIII (FVIII), but published relationships are based on relatively small subsets of available data. Numerous next generation forms of FVIII are being developed (e.g. Fc fusion, PEGylated, and liposomal formulations) and traditional pharmacokinetic scaling of these products would not incorporate the wealth of existing knowledge for current FVIII therapy in humans. We conducted a meta-analysis and developed allometric relationships of FVIII from over 100 PK studies collected from literature. Normalized Wajima curves were used to relate mean FVIII profiles between species. An ‘informed scaling’ approach was derived for predicting first-in-human PK parameters and demonstrated with a case study for an Fc fusion FVIII. NCA values for FVIII PK were well described by the allometric equations CL=6.59·W0.85 and Vss=65.0·W0.97. A subset of studies characterized by two compartment modeling showed strong linearity in scaling of total clearance and central volume, but more variability in distributional clearance and peripheral volume. Wajima curves for FVIII superimposed across species and the disposition of Fc fusion FVIII in humans was well predicted by ‘informed scaling.’ This approach might be generally applicable for predicting human PK of next generational therapeutics.

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Section: Resultsmentioning

confidence: 99%

Allometry of Factor VIII and Informed Scaling of Next-Generation Therapeutic Proteins

Kosloski

Pisal

Mager

et al. 2013

Journal of Pharmaceutical Sciences

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“…The problem of multiple half‐lives is overcome by analysing the data using a model‐independent (non‐compartmental) method. Although model‐dependent analysis may also be used, this will not give the same result (Lee et al , 1990; Morfini et al , 1991; Pascual & Montoro, 1997). A number of different computer software programs are available to analyse the data but may give different estimates of pharmacokinetic parameters.…”

Section: Methodsmentioning

confidence: 99%

The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation

et al. 2006

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SummaryThe revised UKHCDO factor (F) VIII/IX Inhibitor Guidelines (2000) are presented. A schema is proposed for inhibitor surveillance, which varies according to the severity of the haemophilia and the treatment type and regimen used. The methodological and pharmacokinetic approach to inhibitor surveillance in congenital haemophilia has been updated. Factor VIII/IX genotyping of patients is recommended to identify those at increased risk. All patients who develop an inhibitor should be considered for immune tolerance induction (ITI). The decision to attempt ITI for FIX inhibitors must be carefully weighed against the relatively high risk of reactions and the nephrotic syndrome and the relatively low response rate observed in this group. The start of ITI should be deferred until the inhibitor has declined below 10 Bethesda Units/ml, where possible. ITI should continue, even in resistant patients, where it is well tolerated and so long as there is a convincing downward trend in the inhibitor titre. The choice of treatment for bleeding in inhibitor patients is dictated by the severity of the bleed, the current inhibitor titre, the previous anamnestic response to FVIII/IX, the previous clinical response and the side-effect profile of the agents available. We have reviewed novel dose-regimens and modes of administration of FEIBA (factor VIII inhibitor bypassing activity) and recombinant activated FVII (rVIIa) and the extent to which these agents may be used for prophylaxis and surgery. Bleeding in acquired haemophilia is usually treated with FEIBA or rVIIa. Immunosuppressive therapy should be initiated at the time of diagnosis with Prednisolone 1 mg/kg/d ± cyclophosphamide. In the absence of a response to these agents within 6 weeks, second-line therapy with Rituximab, Ciclosporin A, or other multiple-modality regimens may be considered.Keywords: diagnosis, management, factor VIII/IX inhibitors.Since the publication of the previous guideline on the detection and management of factor (F) VIII inhibitors (Hay et al, 2000), significant diagnostic and therapeutic advances have taken place. The UK Haemophilia Doctors Organisation (UKHCDO) has therefore revised and updated those sections of the earlier guideline covering areas of clinical practice which we felt had developed, to define best current practice internationally. Although all sections of the previous guideline have been reviewed, some sections required little revision whereas others required rewriting. For those areas that did not require revision, the reader is referred back to the previous guideline. The evidence-based approach used highlights the need for future clinical trials in areas where current treatment strategies are based on uncontrolled observations or where there is a dichotomy of clinical opinion. MethodsThe guidelines were drafted by the UKHCDO Inhibitor Working Party and circulated to the Executive Committee of the UKHCDO for consultation. Members of UKHCDO and its working parties make an annual declaration of interest to UKHCDO and to their Ho...

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“…Twenty‐seven studies with half‐life data reported between 1990 and 2002 were included [14–17, 48–71], as presented in Table 3. Five of the 27 studies were communicated in abstract form only [57,61,67,68,71]; none was unpublished.…”

Section: Half‐lifementioning

confidence: 99%

Comparative effectiveness of full‐length and B‐domain deleted factor VIII for prophylaxis – a meta‐analysis

Gruppo

Brown

Wilkes³

et al. 2003

Haemophilia

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Recently reported data suggest the possibility of differences in clinical efficacy between full-length factor VIII (FL-FVIII) and B-domain deleted recombinant factor VIII (BDD-rFVIII). To address this question, we conducted a meta-analysis of studies reporting the incidence of bleeding under prophylaxis, as well as studies of FL-FVIII and BDD-rFVIII half-life. The pooled cumulative weekly prophylactic dose of BDD-rFVIII (81.3 +/- 13.8 IU kg(-1) week(-1)) was greater by 36% (P = 0.11) than that of FL-FVIII (60.0 +/- 5.9 IU kg(-1) week(-1)). The pooled incidence of bleeding in BDD-rFVIII recipients [16.8 bleeds per patient year; confidence interval (CI), 9.5-24.2 bleeds per patient year] was more than 2.5-fold larger (P < 0.0005) than that in patients receiving FL-FVIII (6.6 bleeds per patient year; CI, 4.7-8.5 bleeds per patient year). In a multivariate analysis, the incidence rate ratio was 2.10 (CI, 1.98-2.24), indicating that breakthrough bleeding under prophylaxis was more than twice as likely with BDD-rFVIII than FL-FVIII at equivalent doses and ages. The pooled half-life for plasma-derived FL-FVIII (13.7 h; CI, 12.8-14.6 h) was closely similar to that for recombinant FL-FVIII (14.3 h; CI, 13.3-15.4 h). By contrast, the pooled half-life for BDD-rFVIII (11.3 h; CI, 9.9-12.7 h) was shorter by approximately 3 h compared with FL-FVIII. Although the results of the meta-analysis need to be interpreted with caution, the pooled data suggest that breakthrough bleeding under prophylaxis may occur more frequently in patients receiving BDD-rFVIII than FL-FVIII and may at least partly reflect a more abbreviated half-life of BDD-rFVIII. Several biochemical differences between BDD-rFVIII and FL-FVIII may underlie the observed disparities in bleeding incidence and half-life. This meta-analysis should be confirmed by further studies.

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Comparative study of four different pharmacokinetic computer programs: case study of a factor VIII preparation

Cited by 7 publications

References 6 publications

Allometry of Factor VIII and Informed Scaling of Next-Generation Therapeutic Proteins

Allometry of Factor VIII and Informed Scaling of Next-Generation Therapeutic Proteins

The diagnosis and management of factor VIII and IX inhibitors: a guideline from the United Kingdom Haemophilia Centre Doctors Organisation

Comparative effectiveness of full‐length and B‐domain deleted factor VIII for prophylaxis – a meta‐analysis

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