Pharmacokinetics of Once-Daily Intravenous Gentamicin in Term Neonates: Comparison of 4 mg/kg and 5 mg/kg Dosing in Tanzania

Abstract

Gentamicin, a bactericidal aminoglycoside, is used with penicillins to treat neonatal infections. It has a narrow therapeutic index and can cause nephrotoxicity and/or ototoxicity even at therapeutic doses, making serum monitoring essential. In Tanzania, neonates often receive once-daily intravenous gentamicin at a dose of 5mg/kg without monitoring, raising safety concerns since toxicity relates to high, dose-dependent troughs. Although recommended neonatal doses are 4–5mg/kg, reports show 5mg/kg produces high trough concentrations. This study compared the pharmacokinetics of 5mg/kg with 4mg/kg to determine whether the lower dose is safer. Two hundred fifty term neonates with sepsis received intravenous gentamicin once-daily 5mg/kg (n=125) or 4mg/kg (n=125) based on routine clinical practice. Sparse sampling estimated clearance and volume of distribution. In addition, blood samples for peak (30 minutes post-dose) and trough (5 minutes pre-dose) were taken from each patient at steady state (after the fourth dose). Pharmacokinetic parameters were estimated using Python (version 3.12.3), and groups were compared with independent-samples t-tests. Mean steady-state peak gentamicin concentrations were higher with 5 mg/kg (18.80 ± 0.83 µg/mL) than with 4 mg/kg (7.82 ± 0.90 µg/mL), with trough concentrations also elevated (2.52 ± 0.93 vs 1.46 ± 0.36 µg/mL). Clearance was lower with 5mg/kg (0.361 vs 0.575 mL·min⁻¹·kg⁻¹), as was volume of distribution (0.248 vs 0.494 L · kg ^-¹). Once-daily intravenous gentamicin at 5mg/kg results in higher peak and trough concentrations with reduced clearance and distribution. In contrast, 4mg/kg achieves levels within therapeutic ranges. These findings support 4mg/kg as the safer regimen for neonates in Tanzania and similar settings.