# Mechanisms of obesity-induced changes in drug pharmacokinetics

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $54,739

## Abstract

Abstract
Title: Mechanisms of obesity-induced changes in drug pharmacokinetics
Biodisposition profile (pharmacokinetics) of a drug in an individual is governed by drug properties and subject
characteristics. The underlying mechanisms of obesity-induced changes in drug pharmacokinetics have not
been sufficiently studied. Beyond all, obesity is characterized by an alteration of body composition (i.e.,
disproportional increase in fat mass). The prevalence of obesity in the United States nearly doubled from the
early 1960s, and over 1.6 billion people worldwide are considered obese or overweight. Little is known
regarding the effects of obesity on biodisposition of various drug classes, and no consensus on the best dosing
strategy for drugs in obese patients has been established. Attaining therapeutic drug concentration at target
sites is required for successful therapeutic outcome. However, our preliminary study in bariatric surgery
patients found subtherapeutic antibiotic concentration in the subcutaneous adipose tissue at the time of
closure; and similar results were reported by other investigators. This inadequate drug exposure might result in
therapy failure in a specific patient and lead to antibiotic resistance harming the population as a whole.
Consequently, dosing strategies for antibiotics in obese patients are currently suboptimal, which might lead to
treatment failure. Our data also indicate that pharmacokinetics of antibodies (Immunoglobulin G) is also
affected by obesity, which may lead to decreased efficacy and increased toxicity of treatment. We hypothesize
that obesity significantly affects the biodisposition of small-molecule drugs and protein therapeutics. Further,
combining measurements of body composition and pharmacokinetic modeling can be used for predicting drug
exposure in obese patients and facilitate drug selection and optimization of drug dosing in the obese
population. The overall goal of this proposal is to determine how obesity affects pharmacokinetics of beta-
lactam antibiotics and antibodies and to develop mathematical models for predicting drug biodisposition in
obese patients. To achieve this we will: 1) Investigate how obesity affects the pharmacokinetics of small-
molecule drugs using cefoxitin and piperacillin/tazobactam combination in obese human patients, and
investigate the mechanisms of these changes in a preclinical model of obesity; 2) Investigate how obesity
affects the pharmacokinetics of immunoglobulin G (IgG) (a protein therapeutic and skeleton for many
monoclonal antibodies) in obese human patients, and investigate the mechanisms of obesity-induced changes
in pharmacokinetics of IgG and other proteins in a preclinical model. Clinical and preclinical studies will be
accompanied by measurement of the body composition; and translational mathematical models will be
developed for predicting obesity-induced changes in pharmacokinetics of these and other drugs in humans.
The proposed research will fill criti...

## Key facts

- **NIH application ID:** 10388474
- **Project number:** 3R01GM124046-04S1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Leonid Kagan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $54,739
- **Award type:** 3
- **Project period:** 2018-08-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388474

## Citation

> US National Institutes of Health, RePORTER application 10388474, Mechanisms of obesity-induced changes in drug pharmacokinetics (3R01GM124046-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10388474. Licensed CC0.

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