Adjustment of endogenous concentrations in pharmacokinetic modeling.
Purpose: Estimating pharmacokinetic parameters in the presence of an endogenous concentration is not straightforward as cross-reactivity in the analytical methodology prevents differentiation between endogenous and dose-related exogenous concentrations. This article proposes a novel intuitive modeli...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 70; no. 12; pp. 1465 - 1471 |
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| Autores principales: | , |
| Formato: | equations & formulas research tables/charts Journal Article |
| Publicado: |
Springer Nature
Dec2014
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| 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=103914480&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103914480 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Dec2014 vid: 70 iid: 12 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 103914480 99347219 10.1007/s00228-014-1759-x NLM25277161 103914480 ppf: 1465 ppct: 6 formats: fmt: @attributes: type: P tig: atl: Adjustment of endogenous concentrations in pharmacokinetic modeling. aug: au: Bauer, Alexander Wolfsegger, Martin affil: Baxter Innovations GmbH, Vienna Austria sug: subj: Pharmacokinetics Models, Statistical Human Simulations Descriptive Statistics Measurement Error Bias (Research) Regression Data Analysis Software ab: Purpose: Estimating pharmacokinetic parameters in the presence of an endogenous concentration is not straightforward as cross-reactivity in the analytical methodology prevents differentiation between endogenous and dose-related exogenous concentrations. This article proposes a novel intuitive modeling approach which adequately adjusts for the endogenous concentration. Methods: Monte Carlo simulations were carried out based on a two-compartment population pharmacokinetic (PK) model fitted to real data following intravenous administration. A constant and a proportional error model were assumed. The performance of the novel model and the method of straightforward subtraction of the observed baseline concentration from post-dose concentrations were compared in terms of terminal half-life, area under the curve from 0 to infinity, and mean residence time. Results: Mean bias in PK parameters was up to 4.5 times better with the novel model assuming a constant error model and up to 6.5 times better assuming a proportional error model. Conclusions: The simulation study indicates that this novel modeling approach results in less biased and more accurate PK estimates than straightforward subtraction of the observed baseline concentration and overcomes the limitations of previously published approaches. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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