How can we best treat infectious diseases in people with obesity? Hospital pharmacist and Ph.D. researcher Koen van Rhee studied how obesity affects blood levels of two commonly used medicines. He also developed a method for pharmaceutical companies to test new drugs on this patient group.
When you are in pain, you take two 500 mg paracetamol tablets four times a day. That same dosage applies to people with excess weight. Some other medicines, such as antibiotics, are adjusted based on bodyweight.
“The idea is that a heavier person sometimes needs more of a drug to reach the same concentration in the blood. But that’s not always the case,” Van Rhee explains.
“Sometimes, bodyweight has little effect on how a drug is distributed or eliminated, while for other medicines, the impact is significant.” An incorrect adjustment can make a treatment less effective or cause more side effects.
For many medicines, it has not been properly studied whether obesity affects how they work. In his Ph.D. research, Van Rhee focused on the antibiotic ciprofloxacin and the antifungal drug fluconazole.
“With infectious diseases, it is crucial to get the dosage right immediately. For a condition like high blood pressure, it’s less of a problem if the dosage is adjusted later, but in a severe infection, there is usually no time for that.”
Adjusting dosage is not always necessary
One striking finding was that some medicines are incorrectly dosed based on bodyweight. “We found that certain infection treatments are prescribed per kilogram of bodyweight, even though their breakdown is not affected by a higher weight. This means that some patients receive unnecessarily high doses, which can lead to side effects,” Van Rhee says.
On the other hand, there are medicines where weight does matter, but the package insert does not recommend an adjusted dose for people with obesity.
Why has this never been studied before?
Pharmaceutical companies routinely test how medicines work in groups such as children, elderly, and people with liver or kidney problems. However, when registering new drugs, it is not yet mandatory to systematically study the effects of obesity—although this is starting to receive more attention.
“One reason is that obesity was less common in the past,” Van Rhee says. “Now, 13% of the world’s population has obesity, so it has become an important issue to investigate.”
Patients who have had weight-loss surgery: A special research group
To measure how weight affects drug concentration in the body, Van Rhee studied patients who had undergone weight-loss surgery. “This group has a high bodyweight but is otherwise relatively healthy. This allows us to study the effects of obesity without interference from other conditions like kidney problems.”
His research showed that ciprofloxacin, for example, is not broken down more quickly in people with obesity, meaning the standard dosage is safe.
Why obesity affects drug effectiveness in different ways is not always easy to predict, Van Rhee says. “We know that obesity can influence how the body functions. However, the effects vary greatly between medicines, sometimes even among drugs that seem quite similar. That makes it difficult to come up with one general rule.”
Van Rhee argues that the impact of obesity should be routinely studied in drug development. “We already do this for kidney and liver diseases, so why not for obesity?” According to him, this doesn’t have to be a major investment.
“Our computer simulations show that just six to 12 patients with obesity can already provide valuable insights into the correct dosage. That should be feasible for pharmaceutical companies. This way, we can ensure that everyone gets the right dose, regardless of bodyweight.”
Van Rhee will defend his thesis, titled “Unravelling the drivers of antimicrobial pharmacokinetic variability in individuals with obesity and hospitalised patients with multimorbidity,” on 19 February 2025. His supervisor at Leiden University is Professor Catherijne Knibbe.
Written by Manon Boot.
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Source: Leiden University.
