Dissertation

Shaping the pharmacokinetic landscape for renally cleared antibiotics in obesity

The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.

Author: Smit, C.
Date: 11 March 2021
Links: Thesis in Leiden University Scholarly Publications

The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents. Although it is well known that (patho)physiological changes in obese individuals can influence drug pharmacokinetics, implying adjusted doses, there is still a need for specific dose guidelines for many classes of drugs. In this thesis, the pharmacokinetics of the renally cleared antibiotics gentamicin, tobramycin and vancomycin, drugs for which it is well known that both the efficacy and toxicity of these drugs closely relate to blood concentrations, are studied in non-obese and (morbidly) obese adults, adolescents and children. We present practical dose recommendations for the obese adult, paediatric and adolescent populations. Furthermore, some important questions are addressed regarding the pharmacokinetics of drugs in obesity: can we use the lipophilicity of a drug to predict changes in volume of distribution? Which pitfalls have to be considered when using lean body weight as basis for drug dosing? And which methods for estimating glomerular filtration can predict the clearance of renally cleared drugs in obese patients? The work in this thesis provide some important steps in filling the current knowledge gaps regarding the pharmacokinetics of drugs in obesity.