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Hospital pharmacist and Ph.D. researcher Koen van Rhee has made a significant breakthrough in understanding how obesity affects the efficacy of commonly used medications, specifically in the treatment of infectious diseases. Through his research, van Rhee sheds light on how body weight can influence blood levels of antibiotics and antifungal drugs, and the importance of correctly adjusting dosages to avoid ineffective treatment or harmful side effects.
When treating infections, proper medication dosage is crucial. While the standard practice may be to prescribe a consistent dose, such as two 500 mg paracetamol tablets taken four times a day for people of all body weights, van Rhee’s research challenges this one-size-fits-all approach. While some medicines, such as antibiotics, are adjusted according to body weight, others might not require such alterations. For instance, van Rhee’s research specifically examined ciprofloxacin (an antibiotic) and fluconazole (an antifungal). His findings revealed that the way obesity affects the body’s handling of these drugs can differ from one medication to another.
“Sometimes, bodyweight has little effect on how a drug is distributed or eliminated, while for other medicines, the impact is significant,” explains van Rhee. He points out that inaccurate adjustments can either render treatments ineffective or, worse, lead to additional side effects. A key issue is that many medicines have not been properly studied in people with obesity, leaving a gap in understanding how weight affects drug behavior.
In his Ph.D. research, van Rhee found that certain infection treatments, which are often prescribed per kilogram of body weight, were sometimes unnecessarily high for patients with obesity. This could result in harmful side effects. Conversely, other medications for which body weight does matter were not receiving the recommended dose adjustment in some cases.
Van Rhee notes that while pharmaceutical companies do routinely test how medicines work in children, the elderly, and patients with liver or kidney problems, the effects of obesity have not been systematically studied—though this is beginning to change. “One reason is that obesity was less common in the past,” says van Rhee. “Now, with 13% of the world’s population affected by obesity, it is an issue that must be addressed.”
A unique aspect of van Rhee’s research is his study of patients who had undergone weight-loss surgery. These patients have a high body weight but are otherwise healthy, allowing for a clearer understanding of how obesity alone affects the breakdown of medications. Van Rhee found, for example, that ciprofloxacin does not break down more quickly in people with obesity, meaning that the standard dosage remains safe for these patients.
Despite this, van Rhee acknowledges that predicting how obesity affects drug effectiveness remains a challenge. He explains that while obesity can influence how the body processes medications, the effects are not always predictable and can vary widely between different drugs. As a result, there is no universal rule for adjusting dosages based on body weight.
Van Rhee advocates for more comprehensive studies on the impact of obesity during drug development. He points out that similar research is routinely done for patients with kidney and liver diseases. “We already do this for kidney and liver diseases, so why not for obesity?” he asks, noting that conducting such studies need not be expensive or complicated. With simulations showing that as few as six to twelve patients with obesity could provide valuable insights, van Rhee believes this research could easily be incorporated into drug development protocols.
Van Rhee will defend his thesis, titled “Unravelling the Drivers of Antimicrobial Pharmacokinetic Variability in Individuals with Obesity and Hospitalized Patients with Multimorbidity,” on February 19, 2025, at Leiden University, where he is supervised by Professor Catherijne Knibbe.
Disclaimer: The information provided in this article is based on the research findings of Koen van Rhee and is for informational purposes only. It is not intended to serve as medical advice. Always consult a healthcare professional for guidance on medication and treatment decisions.
