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. 2022 Jun 27;24(4):77.
doi: 10.1208/s12248-022-00727-9.

Pharmacokinetics of Gentamicin Components C1, C1a, and C2/C2a/C2b and Subsequent Decline in Glomerular Filtration Rate in Neonates

Hiie Soeorg  1 , Helgi Padari  2 , Karin Kipper  3 , Mari-Liis Ilmoja  4 , Irja Lutsar  5 , Tuuli Metsvaht  2
Affiliations

Pharmacokinetics of Gentamicin Components C1, C1a, and C2/C2a/C2b and Subsequent Decline in Glomerular Filtration Rate in Neonates

Hiie Soeorg et al. AAPS J. .

Abstract

Gentamicin is a commonly used antibiotic in neonates. Its components C1, C1a, C2, C2a, and C2b may have different nephrotoxic potential. We aimed to describe pharmacokinetics and nephrotoxic potential of gentamicin components in a joint model in neonates. Neonates with gestational age ≥ 32 weeks treated with gentamicin blood samples were collected at a steady state. Pharmacokinetics of C1, C1a, and C2/C2a/C2b were modelled in NONMEM and included competitive uptake into kidney proximal tubular cells and decrease in glomerular filtration rate. The nephrotoxic potential of total gentamicin, C1, C1a, and C2/C2a/C2b was evaluated by simulations. A total of 30 neonates (median (range) gestational age 36.4 (32-42) weeks, postnatal age 3 (1-5) days, creatinine value 47.5 (17-78) µmol/L) were included. Pharmacokinetics of all components was best described by a two-compartment model. Clearance of C1 was smaller than clearances of C1a and C2/C2a/C2b, and other parameters were similar. The model with different Km (concentration for which half-maximal uptake into kidney proximal tubular cells is achieved) for C1, C1a, and C2/C2a/C2b (37.5, 18, 15 mg/L) provided a better fit than the model with equal Km (15 mg/L). According to simulations, decrease in glomerular filtration rate in the case of once-daily dosing of 4 mg/kg/day was the largest for C2/C2a/C2b (median (5th and 95th percentile) 0.22% (0.00-8.12%)), followed by total gentamicin (0.20% (0.00-4.10%)), C1a (0.11% (0.00-7.57%)), and C1 (0.04% (0.00-1.55%)). Different gentamicin components C1, C1a, and C2/C2a/C2b exhibited different pharmacokinetic profiles. Once-daily dosing of 4 mg/kg/day results in low nephrotoxicity in neonates, in line with previous studies.

Keywords: Gentamicin; Kidney proximal tubular cells; Neonate; Nephrotoxicity; Pharmacokinetics.

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References

    1. Metsvaht T, Nellis G, Varendi H, Nunn AJ, Graham S, Rieutord A, et al. High variability in the dosing of commonly used antibiotics revealed by a Europe-wide point prevalence study: implications for research and dissemination. BMC Pediatr. 2015;15:41. - DOI
    1. Garrido F, Allegaert K, Arribas C, Villamor E, Raffaeli G, Paniagua M, et al. Variations in antibiotic use and sepsis management in neonatal intensive care units: a European Survey. Antibiotics (Basel). 2021;10(9):1046. - DOI
    1. Kent A, Turner MA, Sharland M, Heath PT. Aminoglycoside toxicity in neonates: something to worry about? Expert Rev Anti Infect Ther. 2014;12(3):319–31. - DOI
    1. Jansen D, Peters E, Heemskerk S, Koster-Kamphuis L, Bouw MP, Roelofs HM, et al. Tubular injury biomarkers to detect gentamicin-induced acute kidney injury in the neonatal intensive care unit. Am J Perinatol. 2016;33(2):180–7. - DOI
    1. Rougier F, Claude D, Maurin M, Sedoglavic A, Ducher M, Corvaisier S, et al. Aminoglycoside nephrotoxicity: modeling, simulation, and control. Antimicrob Agents Chemother. 2003;47(3):1010–6. - DOI

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