25 February 2025

Rethinking Medication Dosages: How Body Weight and Sex Influence Drug Absorption

New research from Leiden University suggests that body weight and sex play a greater role in how medications are absorbed and processed than previously believed. These findings challenge standard dosing guidelines, particularly for overweight patients, and raise concerns about current medical practices.

Catherijne Knibbe, a hospital pharmacist at St. Antonius Hospital and professor of pharmacotherapy, has heard a common complaint from overweight patients: “Paracetamol doesn’t work for me.”

“Painkillers may be ineffective because the dosage isn’t sufficient for someone with a higher body weight,” Knibbe explained. “However, in some cases, weight isn’t the only factor, which is why further research is necessary.”

Despite the widespread use of medications, studies on how weight impacts drug absorption remain limited. Researcher Koen van Rhee from Leiden University investigated the effects of weight on medications for infectious diseases. Collaborating with Knibbe and St. Antonius Hospital, he examined how weight influences drug distribution in the body.

Van Rhee focused on two medications: the antibiotic ciprofloxacin and the antifungal fluconazole. Since no official guidelines exist for adjusting their dosages based on weight, improper dosing can either render the medication ineffective or increase the risk of serious side effects.

The study found that drug absorption is influenced not only by weight but also by sex.

“Men generally weigh more, but that doesn’t always mean they require higher doses,” Van Rhee explained. His research revealed that while men and women of the same weight (80 kg) required different fluconazole doses to reach equivalent blood concentrations, the same variation was not observed with ciprofloxacin.

“This shows that the impact of weight and sex on drug absorption differs depending on the medication,” Van Rhee said.

For patients like Nienke Cnossen, determining the correct medication dosage has been a challenge. Weighing 172 kilograms before undergoing two gastric reduction surgeries, she lost over 100 kilograms. “Life has literally become lighter,” she shared.

Despite her significant weight loss, Cnossen continues to face medical difficulties. 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.

Adjusting medication doses before and after her surgeries has been complex. “Now that I’ve lost weight, how much should I take? Do I absorb medications better or worse?” she questioned. These uncertainties remain unresolved.

Ömrüm Aydin, chair of the Dutch Foundation for Overweight (Nederlandse Stichting Over Gewicht), highlighted the need to address bias in healthcare.

“Breaking the stigma around obesity is crucial to improving medical care for overweight patients,” Aydin said. “If obesity is viewed solely as the patient’s responsibility, there’s little motivation to advance research or ensure adequate treatment coverage.”

Van Rhee hopes his findings will be swiftly integrated into clinical practice. “The advantage of this research is that it can be applied immediately,” he noted. “And large test groups aren’t necessary—55 patients were enough to study two medications.”

Cnossen, now an advocate for overweight patients, regularly engages with doctors to improve healthcare for individuals facing similar challenges. Many of their concerns remain unanswered.

“How does my weight impact surgery? Will painkillers work effectively? What steps can I take myself?” she asked.