Dissertation

Individualization of Drug Clearance Predictions and Dose Regimens in Patients with Obesity Using Pharmacometric Approaches

This thesis aims to develop model-based approaches to optimize drug dosing in patients with overweight and (morbid) obesity.

Author: T. Zhang
Date: 10 March 2026
Links: Thesis in Leiden Repository

It first evaluates commonly accepted assumptions about how obesity affects drug pharmacokinetics (PK), assessing existing evidence on anticipated changes in drug disposition.Building on this foundation, the research applies population PK modeling to investigate how obesity interacts with factors such as age, sex, and renal function, using vancomycin as a case study. Special attention is given to distinguishing the effects of obesity from developmental weight changes and to addressing dosing challenges in hospitalized patients with obesity and renal impairment. Model-based recommendations are proposed to support safer and more effective, target-driven dosing.In addition, physiologically based PK (PBPK) modeling is used to systematically explore how drug-specific properties and patient characteristics influence drug clearance across varying degrees of obesity. Both hepatic metabolism and renal elimination pathways are examined to identify scenarios in which common weight-based dosing strategies are appropriate or require adjustment.Overall, the thesis provides evidence-based insights and practical guidance to improve dosing strategies and support individualized pharmacotherapy in populations with obesity.