Population pharmacokinetic model of subcutaneous fentanyl in older acute care patients.

Purpose: Subcutaneous fentanyl injection is commonly prescribed to manage acute pain in older patients; however, there is a gap in the literature describing the pharmacokinetic parameters for this route of administration in this population. The aim of this study was to develop and evaluate a populat...

Descripción completa

Detalles Bibliográficos
Publicado en:European Journal of Clinical Pharmacology Vol. 77; no. 9; pp. 1357 - 1369
Autores principales: Al-Qurain, Aymen A., Upton, Richard, Williams, Desmond B., Mackenzie, Lorraine, Phillips, Craig, Russell, Patrick T., Tadros, Rami, Roberts, Michael S., Wiese, Michael D.
Formato: research tables/charts Journal Article
Publicado: Springer Nature Sep2021
Acceso en línea:Ver este registro en EBSCOhost
fields @attributes:
  recordID: 1
pdfLink:
plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=151776453&site=ehost-live
header:
  @attributes:
    shortDbName: ccm
    uiTerm: 151776453
    longDbName: CINAHL Complete
    uiTag: AN
  controlInfo:
    bkinfo:
    dissinfo:
    jinfo:
      jid:
        00316970
        NP9
      jtl: European Journal of Clinical Pharmacology
      issn: 00316970
      maglogo: N
    pubinfo:
      dt: Sep2021
      vid: 77
      iid: 9
      pid: 237
      pub: Springer Nature
      place: New York, New York
    artinfo:
      ui:
        151776453
        149610567
        151776453
        151776453
        10.1007/s00228-021-03126-9
        151776453
      ppf: 1357
      ppct: 12
      formats:
        fmt:
          @attributes:
            type: P
      tig:
        atl: Population pharmacokinetic model of subcutaneous fentanyl in older acute care patients.
      aug:
        au:
          Al-Qurain, Aymen A.
          Upton, Richard
          Williams, Desmond B.
          Mackenzie, Lorraine
          Phillips, Craig
          Russell, Patrick T.
          Tadros, Rami
          Roberts, Michael S.
          Wiese, Michael D.
        affil: UniSA: Clinical and Health Sciences, University of South Australia, Adelaide, Australia
      sug:
        subj:
          Fentanyl Pharmacokinetics
          Injections, Subcutaneous
          Fentanyl Administration and Dosage
          Acute Care
          Human
          Chromatography, Liquid
          Mass Spectrometry
          Clinical Assessment Tools
          Creatinine
          Models, Statistical
      ab: Purpose: Subcutaneous fentanyl injection is commonly prescribed to manage acute pain in older patients; however, there is a gap in the literature describing the pharmacokinetic parameters for this route of administration in this population. The aim of this study was to develop and evaluate a population pharmacokinetic model for subcutaneous fentanyl injection in older patients. Methods: Twenty-one patients who received subcutaneous fentanyl injections (50 to 75 μg) were recruited. Fentanyl concentrations were determined using a validated liquid chromatography/tandem mass spectrometry method. A population pharmacokinetic model was developed using non-linear mixed-effects modelling. A base model was selected based on the Akaike information criterion. Age, sex, body weight, number of previous fentanyl doses, number of prescribed medications, creatinine clearance, Charlson Comorbidity Index, Identification of Seniors at Risk score and concurrent use of CYP3A4 inhibitors were covariates considered for inclusion. A p value of < 0.05 was considered statistically significant for inclusion of covariates in the final model by stepwise addition. The simulation performance of the model was assessed by visual predictive check. Results: A one-compartment, first-order absorption with lag time and linear elimination model was the best to fit to the fentanyl concentration data. The absorption rate constant was 0.136 h−1 (between subject variability (BSV), 46%), lag time 0.66 h (BSV 51%), apparent volume of distribution 6.28 L (BSV 30%), and apparent clearance 16.3 L.h−1 (BSV 54%). The Charlson Comorbidity Index was the only covariate included in the final model, where a higher value of the index increased fentanyl exposure and Cmax. Conclusion: This is the first report of subcutaneous fentanyl population pharmacokinetic model to evaluate fentanyl pharmacokinetic in older patients. The between subject variability in clearance and subcutaneous absorption rate was relatively high, and some patients recorded high fentanyl concentrations in the context of their titration to effect.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
    refInfo:
    holdings:
      @attributes:
        islocal: N