Study finds weight and sex affect medication effectiveness
New research from Leiden University suggests that body weight and sex play a larger role in how medications are absorbed and processed than previously thought. The findings indicate that standard dosing guidelines may not always be effective for overweight patients, raising questions about current medical practices.
Catherijne Knibbe, a hospital pharmacist at St. Antonius Hospital and professor of pharmacotherapy, has heard the same complaint from overweight patients many times: “Paracetamol doesn’t work for me.”
“Painkillers don’t always work well because the dose may be insufficient for someone who weighs more,” Knibbe said. “But in some cases, weight isn’t the issue at all. That’s why we are conducting more research.”
Despite the widespread use of medications, there is little research on how weight affects drug absorption. Koen van Rhee, a researcher at Leiden University, studied how medications for infectious diseases work in people with higher body weight. He collaborated with Knibbe and St. Antonius Hospital to analyze the effects of weight on drug distribution in the body.
Van Rhee’s research focused on two medications: the antibiotic ciprofloxacin and the antifungal drug fluconazole. No official guidelines existed for adjusting doses of these drugs based on weight, even though proper dosing is critical. Underdosing can make the medication ineffective, while overdosing increases the risk of serious side effects.
The study found that weight is not the only factor influencing drug absorption—sex also affects how medications work.
“Men are often heavier, but that doesn’t mean they always need higher doses of medication,” Van Rhee said. His study showed that a man and a woman who both weigh 80 kilograms require different doses of fluconazole to reach the same concentration in the blood. However, the same difference was not observed with ciprofloxacin.
“This means that it’s not just about weight or sex—it varies by medication,” Van Rhee explained.
For patients like Nienke Cnossen, getting the right medication dosage has been a challenge. Cnossen, who once weighed 172 kilograms, underwent two gastric reduction surgeries and lost over 100 kilograms. “Life has literally become lighter,” she said.
Despite her weight loss, Cnossen still faces medical challenges. She was eventually diagnosed with Ehlers-Danlos syndrome, a rare connective tissue disorder. “Being overweight didn’t help, but it wasn’t the cause of my condition,” she said.
Finding the right medication doses before and after her surgeries has been difficult. “How much should I take now that I’ve lost weight? Do I absorb it better or worse?” Cnossen said. These questions remain unresolved.
Ömrüm Aydin, chair of the Dutch Foundation for Overweight (Nederlandse Stichting Over Gewicht), emphasized the importance of addressing bias in healthcare.
“It is critical to break the stigma surrounding obesity to improve healthcare for overweight patients,” Aydin said. “If people believe that being overweight is entirely the patient’s fault, there’s little motivation to conduct further research or ensure treatments are covered.”
Van Rhee hopes his findings will be quickly applied in clinical settings. “The great thing about this research is that it can be implemented immediately in practice,” he said. “And we don’t need huge test groups—55 patients are enough to study two medications.”
Cnossen, now an advocate for overweight patients, frequently speaks with doctors to help improve healthcare for people struggling with obesity. Many of their concerns remain unanswered.
“How does my weight affect surgery? Will painkillers work properly? What can I do myself?” she said.
