Population Pharmacokinetic Characteristics of Amikacinin Suspected Cases of Neonatal Sepsisina Low-Resource African Setting: A Prospective Nonrandomized Single-SiteStudy

dc.contributor.authorAmponsah, S.K.
dc.contributor.authorAdjei, G.O.
dc.contributor.authorEnweronu-Laryea, C.
dc.contributor.authorBugyei, K.A.
dc.contributor.authorHadji-Popovski, K.
dc.contributor.authorKurtzhals, J.A.L.
dc.contributor.authorKristensen, K.
dc.date.accessioned2018-11-26T14:52:35Z
dc.date.available2018-11-26T14:52:35Z
dc.date.issued2017-01-03
dc.descriptionArticleen_US
dc.description.abstractBackground: Amikacin exhibits marked pharmacokinetic (PK) variability and is commonly used in Combination with other drugs in the treatment of neonatal sepsis. There is a paucity of amikacin PK Information in neonates from low-resource settings. Objectives: To determine the PK parameters of amikacin, and explore the influence of selected covariates, including coadministration with aminophylline, on amikacin disposition in neonates of African origin. Methods: Neonates with suspected sepsis admitted to an intensive care unit in Accra, Ghana, and treated with amikacin (15mg/kg loading followed by 7.5mg/kg every 12 hours), were recruited. Serum amikacin Concentration was measured at specified times after treatment initiation and analysed using a population PK modelling approach. Results: A total of 419 serum concentrations were available for 247 neonates. Mean (SD) trough amikacin concentration (from samples collected 30 minutes before the fourth dose) among term (n ¼ 25), and preterm (< 37weeks’ gestation n ¼ 36) neonates were 6.2 (3.4) and 9.2 (5.7) mg/mL, respectively (P ¼ 0.02). A 1-compartment model best fitted amikacin disposition, and birth weight was the most important predictor of amikacin clearance (CL) and distribution (V). The population CL and V of amikacin were related as CL (L/h) ¼ 0.153 (birthweight/2.5) 1.31, V(L) ¼ 2.94 (birthweight/2.5)1.18. There was a high between-subject variability (58.9% and 50.7% ) in CL and V, respectively. CL and V were 0.058L/h/kg and 1.15L/kg, respectively, for a mean birth weight of 2.1kg, and the mean half-life (based on 1-compartmentmodel), was 13.7hours. Conclusions: The V and half-life of amikacin in this cohort varied from that reported in non-African populations, and the high trough and low peak amikacin concentrations in both term and preterm neonates suggest strategies to optimize amikacin dosing are required in this population.en_US
dc.identifier.otherhttp://dx.doi.org/10.1016/j.curtheres.2017.01.001
dc.identifier.urihttp://ugspace.ug.edu.gh/handle/123456789/25810
dc.language.isoenen_US
dc.publisherElsevier Inc.en_US
dc.subjectaminoglycosideen_US
dc.subjectclearanceen_US
dc.subjectdistributionen_US
dc.subjectsepsisen_US
dc.titlePopulation Pharmacokinetic Characteristics of Amikacinin Suspected Cases of Neonatal Sepsisina Low-Resource African Setting: A Prospective Nonrandomized Single-SiteStudyen_US
dc.typeArticleen_US

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