Model‐Based Evaluation of Linear Limited and Bayesian Sparse Sampling for Therapeutic Monitoring of Recombinant Coagulation Factor IX.

Dosing of coagulation factor products is mainly determined based on a patient's body weight; however, several studies have reported high interindividual variability in their pharmacokinetics (PK). The objective of this study was to develop and evaluate 2 sparse sampling methods for the estimation of...

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Publicado en:Journal of Clinical Pharmacology Vol. 60; no. 11; pp. 1453 - 1461
Autores principales: Tegenge, Million A., Mahmood, Iftekhar
Formato: equations & formulas research tables/charts Journal Article
Publicado: Wiley-Blackwell Nov2020
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: Journal of Clinical Pharmacology
      issn: 00912700
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      dt: Nov2020
      vid: 60
      iid: 11
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1002/jcph.1651
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        atl: Model‐Based Evaluation of Linear Limited and Bayesian Sparse Sampling for Therapeutic Monitoring of Recombinant Coagulation Factor IX.
      aug:
        au:
          Tegenge, Million A.
          Mahmood, Iftekhar
        affil: Office of Biostatistics & Epidemiology, Center for Biologics Evaluation and Research, US Food & Drug Administration, Silver Spring Maryland,, USA
      sug:
        subj:
          Blood Coagulation Factors Administration and Dosage
          Blood Coagulation Factors Pharmacokinetics
          Drug Monitoring Methods
          Models, Statistical
          Human
          Adolescence
          Adult
          Blood Specimen Collection
          Dose-Response Relationship, Drug
          Adolescent: 13-18 years
          Adult: 19-44 years
      ab: Dosing of coagulation factor products is mainly determined based on a patient's body weight; however, several studies have reported high interindividual variability in their pharmacokinetics (PK). The objective of this study was to develop and evaluate 2 sparse sampling methods for the estimation of AUC of recombinant factor IX (BeneFIX) as proof of concept for dose individualization. A population pharmacokinetic model was used to generate the plasma factor IX activity‐versus‐time data. The linear limited sampling model (LLSM) was developed based on the correlation of factor IX activity versus AUC0‐72 hours following screening of several blood sampling times in adolescent and adult subjects (n = 90 subjects). Factor IX trough concentrations were predicted from a relationship established from AUC versus factor IX activity measured 72 hours postdosing. Using the best selected sampling time, the LLSM and Bayesian model were validated in separate data sets (n = 75 subjects). Using the LLSM and Bayesian analysis, a blood sample at 24 hours predicted AUC with bias and root mean square error < 5% and < 15%, respectively. The predicted trough concentrations were ≥1 IU/dL in 99% and 100% of subjects by the LLSM and Bayesian model, respectively. The average factor IX dose for a target AUC of 800 IU·h/dL was 61, 60, and 63 IU/kg using the extensive (reference), LLSM and Bayesian model, respectively. Overall, the AUC, trough concentrations and individualized dosing of recombinant factor IX could be reasonably predicted using the LLSM and Bayesian model.
      pubtype: Academic Journal
      doctype:
        equations & formulas
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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