Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-Physiological Function for Maturation in Glomerular Filtration

Document Type

Article

Publication Date

10-2014

Abstract

PURPOSE:

Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults.

METHODS:

In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tobramycin and vancomycin collected in 1,760 patients (age 1 day-18 years, bodyweight 415 g-85 kg), a distinction was made between drug-specific and system-specific information. Since the maturational model for clearance is considered to contain system-specific information on the developmental changes in GFR, one GFR maturational function was derived for all three drugs.

RESULTS:

Simultaneous analysis of these three drugs showed that maturation of GFR mediated clearance from preterm neonates to adults was best described by a bodyweight-dependent exponent (BDE) function with an exponent varying from 1.4 in neonates to 1.0 in adults (ClGFR = Cldrug*(BW/4 kg)(BDE) with BDE = 2.23*BW(-0.065)). Population clearance values (Cldrug) for gentamicin, tobramycin and vancomycin were 0.21, 0.28 and 0.39 L/h for a full term neonate of 4 kg, respectively.

DISCUSSION:

Based on an integrated analysis of gentamicin, tobramycin and vancomycin, a semi-physiological function for GFR mediated clearance was derived that can potentially be used to establish evidence based dosing regimens of renally excreted drugs in children.

DOI

10.1007/s11095-014-1361-z

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