Clinical pharmacokinetics of aminoglycosides in the neonate: a review.
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 (t(1/2)), 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 t(1/2) 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.


CONCLUSIONS
The maturation of the kidney governs the pharmacokinetics of aminoglycosides in the infant. Cl and t(1/2) 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.
Pacifici
Gian Maria
GM
Department of Neurosciences, Section of Pharmacology, University of Pisa Medical School, Pisa, Italy. pacifici@biomed.unipi.it
D000583:Amikacin / Q000097:blood / Q000493:pharmacokinetics; D000617:Aminoglycosides / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D001724:Birth Weight; D004334:Drug Administration Schedule; D005839:Gentamicins / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007231:Infant, Newborn; D009428:Netilmicin / Q000097:blood / Q000493:pharmacokinetics; D014031:Tobramycin / Q000097:blood / Q000493:pharmacokinetics
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D009428:Netilmicin; D000583:Amikacin; D014031:Tobramycin