EC Pharmacology And Toxicology

Gentamicin, an aminoglycoside antibiotic, is widely used in neonatal intensive care units (NICUs) for its efficacy against Gram-negative pathogens. However, its pharmacokinetics (PK) and pharmacodynamics (PD) are influenced by neonatal physiology, necessitating tailored dosing strategies. This review examines the comparative efficacy and safety of extended-interval dosing (EID) versus traditional dosing (TDD) in premature and term neonates. It also evaluates the role of PK/PD principles, particularly therapeutic drug monitoring (TDM) and the area under the curve to minimum inhibitory concentration (AUC/MIC) ratio, in optimizing gentamicin therapy. EID demonstrates superior efficacy and safety by achieving optimal Cmax/MIC ratios and reducing nephrotoxicity and ototoxicity risks, making it the preferred regimen in most neonatal scenarios. Future integration of advanced pharmacometric models and biomarkers promises further improvement in individualizing gentamicin dosing.

 Keywords: Extended-Interval Dosing; Traditional Dosing; Gentamicin; Neonates; Dosing Optimization; Pharmacokinetics; Pharmacodynamics; Nephrotoxicity; Ototoxicity; Therapeutic Drug Monitoring

1. Mulhall A., et al. “Pharmacokinetics of gentamicin in neonates”. Archives of Disease in Childhood 10 (1983): 784-787.
2. Kearns GL., et al. “Developmental pharmacology—drug disposition, action, and therapy in infants and children”. New England Journal of Medicine 12 (2003): 1157-1167.
3. Dersch-Mills D., et al. “Gentamicin extended-interval dosing in neonatal intensive care: A systematic review”. Pediatric Drugs 1 (2018): 65-77.
4. Begg EJ and Barclay ML. “Aminoglycosides—50 years on”. British Journal of Clinical Pharmacology 6 (1995): 597-603.
5. Sherwin CM., et al. “Individualized gentamicin dosing in neonates: A pharmacokinetic/pharmacodynamic approach”. Clinical Therapeutics 11 (2009): 2849.
6. Khaled Alfaify., et al. “Pharmacokinetics. 6 for optimizing the dose of gentamicin in neonates”. LAP Lambert Academic Publishing (2012).
7. Allegaert K and van den Anker JN. “Neonatal drug therapy: the first frontier of therapeutics for children”. Clinical Pharmacology and Therapeutics 3 (2015): 288-297.
8. Rao SC., et al. “Gentamicin extended-interval dosing in neonates: A meta-analysis”. Archives of Disease in Childhood: Fetal and Neonatal Edition 3 (2016): F269-F274.
9. Lopez Sastre JB., et al. “Neonatal sepsis of early onset: A multicenter study”. Journal of Perinatal Medicine 4 (2002): 299-307.
10. Jacqz-Aigrain E., et al. “Developmental pharmacology: drug disposition, action, and therapy in infants and children”. Pediatric Clinics of North America 1 (1997): 15-26.
11. Schwartz RH., et al. “Ototoxicity induced by aminoglycoside antibiotics in pediatric patients”. Pediatrics 4 (1977): 582-586.
12. Weiss M., et al. “Pharmacokinetics of gentamicin in neonates: Systematic review and development of a new model”. Clinical Pharmacokinetics 4 (2009): 241-257.
13. van den Anker JN., et al. “Once-daily dosing of gentamicin in neonates: safety and efficacy”. Pediatric Infectious Disease Journal5 (2003): 374-379.
14. Anderson BJ and Holford NH. “Mechanism-based concepts of size and maturity in pharmacokinetics”. Annual Review of Pharmacology and Toxicology 48 (2008): 303-332.
15. Sherwin CM., et al. “Optimal antimicrobial dosing strategies for neonates: Challenges in clinical practice”. Clinical Pharmacology and Therapeutics 5 (2014): 483-493.