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Clinical pharmacokinetics of aminoglycosides in the neonate: a review

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Sepsis is common in neonates and is a major cause of morbidity and mortality. Sixty percent of preterm neonates receive at least one antibiotic, and 43% of the antibiotics administered to these neonates are aminoglycosides. The clearance (Cl), serum half-life (t1/2), and volume of distribution (Vd) of aminoglycosides change during the neonatal life, and the pharmacokinetics of aminoglycosides need to be studied in neonates in order to optimise therapy with these drugs.

Objective

The aim of this work is to review the published data on the pharmacokinetics of aminoglycosides in order to provide a critical analysis of the literature that can be a useful tool in the hands of physicians.

Methods

The bibliographic search was performed electronically using PubMed, as the search engine, through July 11th, 2008. Firstly, a Medline search was performed with the keywords “pharmacokinetics of aminoglycosides in neonates” with the limit of “human”. Other Medline searches were performed with the keywords “pharmacokinetics of … in neonates” followed by the name of the aminoglycosides: amikacin, gentamicin, netilmicin and tobramycin. In addition, the book Neofax: A Manual of Drugs Used in Neonatal Care by Young and Mangum (Thomson Healthcare, 2007) was consulted.

Results

The aminoglycosides are mainly eliminated by the kidney, and their elimination rates are reduced at birth. As a consequence Cl is reduced and t1/2 is prolonged in the neonate as compared to more mature infants. The high body-water content of the neonate results in a large Vd of aminoglycosides as these drugs are fairly water soluble. Postnatal development is an important factor in the maturation of the neonate, and as postnatal age proceeds, Cl of aminoglycosides increases.

Conclusion

The maturation of the kidney governs the pharmacokinetics of aminoglycosides in the infant. Cl and t1/2 are influenced by development, and this must be taken into consideration when planning a dosage regimen with aminoglycosides in the neonate. Aminoglycosides are fairly water soluble, and the larger water content of neonates yields a larger Vd in these patients.

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Acknowledgements

This work has been supported by the Ministry of the University and Scientific and Technological Research (Rome, Italy).

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  1. Department of Neurosciences, Section of Pharmacology, University of Pisa Medical School, Via Roma 55, I-56126, Pisa, Italy

    Gian Maria Pacifici

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Pacifici, G.M. Clinical pharmacokinetics of aminoglycosides in the neonate: a review. Eur J Clin Pharmacol 65, 419–427 (2009). https://doi.org/10.1007/s00228-008-0599-y

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