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ABSTRACT: Purpose
Tobramycin is an aminoglycoside antibiotic of which the 24 h exposure correlates with efficacy. Recently, we found that clearance of the aminoglycoside gentamicin correlates with total body weight (TBW). In this study, we investigate the full pharmacokinetic profile of tobramycin in obese and non-obese individuals with normal renal function.Methods
Morbidly obese individuals (n?=?20) undergoing bariatric surgery and non-obese healthy volunteers (n?=?8), with TBW ranging 57-194 kg, received an IV dose of tobramycin with plasma concentrations measured over 24 h (n?=?10 per individual). Statistical analysis, modelling and simulations were performed using NONMEM.Results
In a two-compartment model, TBW was the best predictor for central volume of distribution (p?ConclusionsIn obese and non-obese individuals with normal renal function, renal function estimates such as MDRD were identified as best predictors for tobramycin clearance, which may imply that other processes are involved in clearance of tobramycin versus gentamicin. To ensure similar exposure across body weights, we propose a MDRD-based dosing nomogram for obese patients.
SUBMITTER: Smit C
PROVIDER: S-EPMC6542779 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
Smit Cornelis C Wasmann Roeland E RE Wiezer Marinus J MJ van Dongen Hendricus P A HPA Mouton Johan W JW Brüggemann Roger J M RJM Knibbe Catherijne A J CAJ
Pharmaceutical research 20190530 8
<h4>Purpose</h4>Tobramycin is an aminoglycoside antibiotic of which the 24 h exposure correlates with efficacy. Recently, we found that clearance of the aminoglycoside gentamicin correlates with total body weight (TBW). In this study, we investigate the full pharmacokinetic profile of tobramycin in obese and non-obese individuals with normal renal function.<h4>Methods</h4>Morbidly obese individuals (n = 20) undergoing bariatric surgery and non-obese healthy volunteers (n = 8), with TBW ranging 5 ...[more]