A Gentamicin Pharmacokinetic Population Model and Once‐Daily Dosing Algorithm for Neonates

Abstract

This dosing algorithm provides a new approach for determining initial gentamicin dosing regimens in neonates; however, clinical validation is required.

Acute effects of gentamicin on glomerular and tubular functions in preterm neonates

“…The gentamicin dosing schedule used was that of Neofax (2002) [8], which is a widely used reference for neonatal drug dosing. We observed an inverse correlation between gentamicin trough and peak levels and gestational age, as has been reported previously [11]. Therapeutic serum trough and peak gentamicin levels were found in 91.8 and 63.9% of the neonate patients, respectively.…”

A simple, weight-based, extended-interval gentamicin dosage protocol for neonates

“…All the comparative studies did show EID protocols to be superior to MDD protocols in providing fewer elevated troughs, fewer subtarget peaks, and fewer dosage adjustments when these were reported. [15][16][17][18][19][20][21][22]24 With respect to these three elements, our protocol produced similar results. The percentage of patients requiring dosage adjustments in these studies ranged from 0% to 13%, compared with 7% in our evaluation.…”

“…Since the 1998 survey, 14 several viable options have been evaluated; however, no clear consensus exists as to the optimal dosage regimen for neonates. [15][16][17][18][19][20][21][22] With only a few clinical trials directly comparing these protocols, 23 clinicians must decide which protocols might best fit the needs of their patient population and institution.…”

Two nomograms for determining extended-dosing intervals for gentamicin in neonates

“…18 A fixed dose of 4 mg/kg was then chosen based on the analysis of current dosing protocols. [1][2][3][4][5][6] Individual elimination-rate constants (k) were determined for dosing intervals of 24, 36, and 48 hours that would produce steady-state trough gentamicin concentrations of 0.5 or 1 mg/L at 0.5 hour before the next dose. The following steady-state equation (equation 1) was used to determine these k values by iteration using Excel (Microsoft Corporation, Redmond, WA):…”

“…[1][2][3][4][5][6][7][8] The standard approach used to adjust doses and dosing intervals involves collecting both serum or plasma peak and trough concentrations of an aminoglycoside. This approach, while reasonably accurate, relies on the collection of two concentrations that coincide closely with the administration of one or two doses and therefore can lead to errors because of the need for additional blood collections and often short windows of time in which to collect these samples.…”