Tobramycin Clearance Is Best Described by Renal Function Estimates in Obese and Non-obese Individuals: Results of a Prospective Rich Sampling Pharmacokinetic Study
Publication year
2019Source
Pharmaceutical Research, 36, 8, (2019), pp. 112ISSN
Publication type
Article / Letter to editor

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Organization
Clinical Pharmacy
Journal title
Pharmaceutical Research
Volume
vol. 36
Issue
iss. 8
Page start
p. 112
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health SciencesAbstract
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 < 0.001). For clearance, MDRD (de-indexed for body surface area) was identified as best covariate (p < 0.001), and was superior over TBW ((p < 0.05). Other renal function estimates (24 h urine GFR and de-indexed CKD-EPI) led to similar results as MDRD (all p < 0.001)). CONCLUSIONS: In 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.
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- Academic publications [227864]
- Electronic publications [107344]
- Faculty of Medical Sciences [86218]
- Open Access publications [76463]
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