A Neonatal Amikacin Covariate Model Can Be Used to Predict Ontogeny of Other Drugs Eliminated Through Glomerular Filtration in Neonates

PURPOSERecently, a covariate model characterizing developmental changes in clearance of amikacin in neonates has been developed using birth bodyweight and postnatal age. The aim of this study was to evaluate whether this covariate model can be used to predict maturation in clearance of other renally excreted drugs.METHODSFive different neonatal datasets were available on netilmicin, vancomycin, tobramycin and gentamicin. The extensively validated covariate model for amikacin clearance was used to predict clearance of these drugs. In addition, independent reference models were developed based on a systematic covariate analysis.RESULTSThe descriptive and predictive properties of the models developed using the amikacin covariate model were good, and fairly similar to the independent reference models (goodness-of-fit plots, NPDE). Moreover, similar clearance values were obtained for both approaches. Finally, the same covariates as in the covariate model of amikacin, i.e. birth bodyweight and postnatal age, were identified on clearance in the independent reference models.CONCLUSIONSThis study shows that pediatric covariate models may contain physiological information since information derived from one drug can be used to describe other drugs. This semi-physiological approach may be used to optimize sparse data analysis and to derive individualized dosing algorithms for drugs in children.

Allegaert, Karel (author)
Sherwin, Catherine M T (author)
Nielsen, Elisabet IUppsala universitet,Institutionen för farmaceutisk biovetenskap,Farmakometri(Swepub:uu)elnie838 (author)
de Hoog, Matthijs (author)
van den Anker, Johannes N (author)
Danhof, Meindert (author)
Knibbe, Catherijne A J (author)
Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

In:Pharmaceutical research: Springer Science and Business Media LLC31:3, s. 754-7670724-87411573-904X

By the author/editor: De Cock, Roosmar ...; Allegaert, Karel; Sherwin, Catheri ...; Nielsen, Elisabe ...; de Hoog, Matthij ...; van den Anker, J ...; show more...; Danhof, Meindert; Knibbe, Catherij ...; show less...

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