ABSTRACT Treatment with an aminoglycoside is essential in proved or suspected Gram-negative sepsis in the neonate. Gentamicin is the most common aminoglycoside used in newborn infants. Several gentamicin therapeutic schedules have been used in the treatment of the neonate and they differ for the dose and for the interval between doses. Peak gentamicin concentration from 5 to 12 µg/ml and trough gentamicin concentration <2 µg/ml are appropriate in the treatment of neonatal Gram-negative sepsis. The aim of this study is to review the published data on the pharmacokinetics of gentamicin in the neonate, in order to provide a critical analysis of literature that can be useful information in the hands of physicians. “Once-daily” gentamicin dosing regimen of 4 mg/kg gives higher peak and lower trough concentrations than 2.5 mg/kg every 12 h. Extending the interval dosing to 24-48 h, depending on the gestational age, and increasing the gentamicin dose to 5 mg/kg generate peak and trough concentrations <12 and <2 µg/ml, respectively which are the expected values. The kinetic parameters of gentamicin vary with the gestational age. The half-life (t1/2) decreases as the development proceeds whereas the clearance (Cl) has an opposite trend. Such variations reflect the renal maturation as gentamicin is mainly eliminated by the kidney. Gentamicin is fairly water soluble and the body water content is larger in the premature than in the term infant. Thus, the volume of distribution (Vd) is larger in the premature than in the term neonate. The pharmacokinetic parameters of gentamicin range from 6.2 to 14.6 h (t1/2); from 0.38 to 1.52 ml/min/kg (Cl); from 0.35 to 1.23 l/kg (Vd); and from 50.6 to 88.4 µg.h/ml (area under the curve; AUC). The “Once-daily” regimen of gentamicin is preferred to the “twice-daily” regimen. Increasing gentamicin dosing to 5 mg/kg and extending the dosing interval to 24-48 h is a new gentamicin regimen that attracts the attention of physicians. Maturation of kidney governs the pharmacokinetics of gentamicin in the infant. t1/2 decreases and Cl increases as the development proceeds and this must be taken into consideration when planning a dosage regimen with gentamicin in the neonate.
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