Altered gentamicin pharmacokinetics in term neonates undergoing controlled hypothermia

British Journal of Clinical Pharmacology
Yuma A BijleveldPharmaCool study group

Abstract

Little is known about the pharmacokinetic (PK) properties of gentamicin in newborns undergoing controlled hypothermia after suffering from hypoxic−ischaemic encephalopathy due to perinatal asphyxia. This study prospectively evaluates and describes the population PK of gentamicin in these patients Demographic, clinical and laboratory data of patients included in a multicentre prospective observational cohort study (the ‘PharmaCool Study’) were collected. A non-linear mixed-effects regression analysis (nonmem®) was performed to describe the population PK of gentamicin. The most optimal dosing regimen was evaluated based on simulations of the final model. A total of 47 patients receiving gentamicin were included in the analysis. The PK were best described by an allometric two compartment model with gestational age (GA) as a covariate on clearance (CL). During hypothermia the CL of a typical patient (3 kg, GA 40 weeks, 2 days post-natal age (PNA)) was 0.06 l kg−1 h−1 (inter-individual variability (IIV) 26.6%) and volume of distribution of the central compartment (Vc) was 0.46 l kg−1 (IIV 40.8%). CL was constant during hypothermia and rewarming, but increased by 29% after reaching normothermia (>96 h PNA). This study describes the P...Continue Reading

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Citations

May 5, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Raffaele CoppiniKarel Allegaert
Sep 15, 2016·Expert Opinion on Drug Metabolism & Toxicology·Anne SmitsKarel Allegaert
Jan 31, 2018·Antimicrobial Agents and Chemotherapy·Yuma A BijleveldUNKNOWN PharmaCool Study Group
Oct 11, 2017·Antimicrobial Agents and Chemotherapy·Sinziana CristeaKarel Allegaert
Feb 15, 2019·PloS One·Laurent M A FaviéUNKNOWN PharmaCool study group
May 19, 2019·Journal of Clinical Pharmacy and Therapeutics·Mateja CrcekMojca Kerec Kos
May 31, 2017·Clinical Pharmacology and Therapeutics·Y A BijleveldUNKNOWN PharmaCool Study Group
Oct 13, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Heidi J MurphyJennifer G Jetton
Jul 12, 2017·Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies·Philip E Empey
Apr 15, 2021·Journal of Perinatology : Official Journal of the California Perinatal Association·Adrianne R BischoffRegan E Giesinger

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