An extended interval dosing method for gentamicin in neonates

• Published in: Journal of antimicrobial chemotherapy Vol. 48; no. 6; pp. 887 - 893
• Main Authors: Stickland, M. D., Kirkpatrick, C. M. J., Begg, E. J., Duffull, S. B., Oddie, S. J., Darlow, B. A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.12.2001; Oxford Publishing Limited (England)
• Subjects: Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Area Under Curve; Biological and medical sciences; Drug Administration Schedule; Drug Monitoring - methods; Gentamicins - administration & dosage; Gentamicins - pharmacokinetics; Humans; Infant, Newborn - blood; Linear Models; Medical sciences; Pharmacology. Drug treatments; Prospective Studies; Human; Intravenous administration; Toxicity; Gentamicin; Biological activity; Antibiotic; Chemotherapy; Absorption; Newborn; Treatment; Aminoglycoside; Antibacterial agent; Pharmacokinetics
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/48.6.887

Traditional gentamicin dosing every 8–24 h depending on age and weight in neonates does not provide the ideal concentration–time profile to both optimize the concentration-dependent killing by aminoglycosides and minimize toxicity. Fifty-three neonates were audited prospectively while receiving gentamicin 2.5 mg/kg every 8–24 h, aiming for peak concentrations (Cmax) of 6–10 mg/L and trough concentrations (Cmin) <2 mg/L. After the first dose, the mean (± s.d.) Cmax was 5.5 ± 0.7 mg/L with sub-therapeutic concentrations (<6 mg/L) in 62% of patients, while the mean Cmin was >2 mg/L in 15% of the neonates. After the third dose the Cmax was 7.5 ± 1.5 mg/L, with 17% <6 mg/L, whereas the mean Cmin was 2.2 ± 1.1 mg/L with 49% of values >2 mg/L. An extended interval dosing method (24, 36 and 48 h) for infant weights of 0.75–5 kg was developed by simulation, and audited prospectively in 51 neonates. Prospective analysis of the extended interval dosing method showed a mean Cmax after the first dose of 13.1 ± 3.6 mg/L, while the mean Cmin was 0.7 ± 0.6 mg/L. Seventy-eight per cent had Cmax of >10 mg/L after the first dose. The mean area under the concentration versus time curve AUC0–24 was 93 mg•h/L (target = 100 mg•h/L). The extended interval dosing achieved higher Cmax values while ensuring that overall exposure per 24 h was acceptable. Prospective testing of the method demonstrated good predictive ability.