The impact of frailty on pharmacokinetics in older people: using gentamicin population pharmacokinetic modeling to investigate changes in renal drug clearance by glomerular filtration.
Purpose: Frailty, a multifactorial biological syndrome characterized by a cumulative dysregulation of physiological processes, is associated with changes in pharmacokinetics and pharmacodynamics. The aim of this study was to quantify the effect of frailty on glomerular filtration of drugs, using the...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 70; no. 5; pp. 549 - 556 |
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| Autores principales: | , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
May2014
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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=104062926&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104062926 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: May2014 vid: 70 iid: 5 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104062926 95446666 10.1007/s00228-014-1652-7 NLM24522409 104062926 ppf: 549 ppct: 7 formats: fmt: @attributes: type: P tig: atl: The impact of frailty on pharmacokinetics in older people: using gentamicin population pharmacokinetic modeling to investigate changes in renal drug clearance by glomerular filtration. aug: au: Johnston, Claire Hilmer, Sarah McLachlan, Andrew Matthews, Slade Carroll, Peter Kirkpatrick, Carl affil: Sydney Medical School, University of Sydney, Sydney NSW Australia sug: subj: Gentamicins Pharmacokinetics Frailty Syndrome Complications Glomerular Filtration Rate Kidney Physiology Frail Elderly Prospective Studies Observational Methods Inpatients Human Male Female Aged Aged, 80 and Over Data Analysis Software Models, Statistical kappa Statistic Parametric Statistics Analysis of Covariance Linear Regression Confidence Intervals Aged: 65+ years Aged, 80 & over Male Female ab: Purpose: Frailty, a multifactorial biological syndrome characterized by a cumulative dysregulation of physiological processes, is associated with changes in pharmacokinetics and pharmacodynamics. The aim of this study was to quantify the effect of frailty on glomerular filtration of drugs, using the probe drug gentamicin. Methods: Gentamicin concentrations and clinical data including the Reported Edmonton Frail Scale score were pooled from two prospective observational inpatient studies, one on prophylactic gentamicin for urologic surgery and one on therapeutic gentamicin for the empiric treatment of sepsis. Population pharmacokinetic modeling was performed using non-linear mixed effects modeling (NONMEM program) to determine the impact of frailty on gentamicin clearance. Results: A one-compartment linear pharmacokinetic model best described the data and the addition of frailty to the model reduced the random variability in gentamicin clearance by 12 % after adjustment for renal function (estimated creatinine clearance using lean body weight) and lean body weight. Frail patients had an approximately 12 % lower (bootstrapping results: 14 % median) gentamicin clearance than non-frail patients (calculated as a fractional effect of frailty). Conclusions: Frailty may independently predict reduced clearance of gentamicin in older patients. Frailty could be considered in the development of dosing guidelines for drugs that undergo significant excretion through glomerular filtration. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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