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Development and Eva...
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Germovsek, EvaUCL, Inst Child Hlth, Inflammat Infect & Rheumatol Sect, London, England.
(författare)
Development and Evaluation of a Gentamicin Pharmacokinetic Model That Facilitates Opportunistic Gentamicin Therapeutic Drug Monitoring in Neonates and Infants
- Artikel/kapitelEngelska2016
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Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-303286
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-303286URI
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https://doi.org/10.1128/AAC.00577-16DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Trough gentamicin therapeutic drug monitoring (TDM) is time-consuming, disruptive to neonatal clinical care, and a patient safety issue. Bayesian models could allow TDM to be performed opportunistically at the time of routine blood tests. This study aimed to develop and prospectively evaluate a new gentamicin model and a novel Bayesian computer tool (neoGent) for TDM use in neonatal intensive care. We also evaluated model performance for predicting peak concentrations and the area under the concentration-time curve from time 0 h to time t h (AUC(0-t)). A pharmacokinetic meta-analysis was performed on pooled data from three studies (1,325 concentrations from 205 patients). A 3-compartment model was used with the following covariates: allometric weight scaling, postmenstrual and postnatal age, and serum creatinine concentration. Final parameter estimates (standard errors) were as follows: clearance, 6.2 (0.3) liters/h/70 kg of body weight; central volume (V), 26.5 (0.6) liters/70 kg; intercompartmental disposition (Q), 2.2 (0.3) liters/h/70 kg; peripheral volume V2, 21.2 (1.5) liters/70 kg; intercompartmental disposition (Q2), 0.3 (0.05) liters/h/70 kg; peripheral volume V3, 148 (52.0) liters/70 kg. The model's ability to predict trough concentrations from an opportunistic sample was evaluated in a prospective observational cohort study that included data from 163 patients and 483 concentrations collected in five hospitals. Unbiased trough predictions were obtained; the median (95% confidence interval [CI]) prediction error was 0.0004 (-1.07, 0.84) mg/liter. Results also showed that peaks and AUC(0-t) values could be predicted (from one randomly selected sample) with little bias but relative imprecision, with median (95% CI) prediction errors being 0.16 (-4.76, 5.01) mg/liter and 10.8 (-24.9, 62.2) mg center dot h/liter, respectively. neoGent was implemented in R/NONMEM and in the freely available TDMx software.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Kent, AlisonSt Georges Univ London, Inst Infect & Immun, Paediat Infect Dis Res Grp, London, England.
(författare)
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Metsvaht, TuuliUniv Tartu, Dept Microbiol, Tartu, Estonia.
(författare)
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Lutsar, IrjaUniv Tartu, Dept Microbiol, Tartu, Estonia.
(författare)
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Klein, NigelUCL, Inst Child Hlth, Inflammat Infect & Rheumatol Sect, London, England.
(författare)
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Turner, Mark A.Univ Liverpool, Inst Translat Med, Dept Womens & Childrens Hlth, Liverpool, Merseyside, England.
(författare)
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Sharland, MikeSt Georges Univ London, Inst Infect & Immun, Paediat Infect Dis Res Grp, London, England.
(författare)
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Nielsen, Elisabet I.Uppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)elnie838
(författare)
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Heath, Paul T.St Georges Univ London, Inst Infect & Immun, Paediat Infect Dis Res Grp, London, England.
(författare)
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Standing, Joseph F.UCL, Inst Child Hlth, Inflammat Infect & Rheumatol Sect, London, England.
(författare)
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UCL, Inst Child Hlth, Inflammat Infect & Rheumatol Sect, London, England.St Georges Univ London, Inst Infect & Immun, Paediat Infect Dis Res Grp, London, England.
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Antimicrobial Agents and Chemotherapy60:8, s. 4869-48770066-48041098-6596
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Germovsek, Eva
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Kent, Alison
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Metsvaht, Tuuli
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Lutsar, Irja
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Klein, Nigel
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Turner, Mark A.
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Sharland, Mike
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Nielsen, Elisabe ...
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Heath, Paul T.
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Standing, Joseph ...
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