The surgery was a success, but a question loomed after the procedure: given that the patient was obese, what was the right antibiotic dose? “The thought was, well, she's twice as big as a normal person, so we'll give her twice the dose,” says Aaron Cook, a clinical pharmacy specialist at the University of Kentucky in Lexington. “For that drug, levofloxacin, there's just no information to go on, no dosage recommendation for obese patients.”

The patient fared well, but such conundrums are becoming increasingly common as obesity rates rise around the globe. Just a month ago, researchers released new figures estimating that the US will see an additional 65 million obese individuals by 2030 (Lancet 378, 815–825, 2011). Already in the country approximately one in three adults and one in six children are obese—a condition that can precipitate heart disease, diabetes, respiratory failure and other illnesses that often require medication. But experts say that merely doubling the dose isn't the solution because the physiological changes that accompany obesity, such as increases in the volume of blood pumped by the heart and fat mass, can in turn lead to changes drug absorption and metabolism.

Chandrahas Sahajwalla, who conducts pharmacological research at a US Food and Drug Administration (FDA) office in Silver Spring, Maryland, has tried calling attention to the paucity of information in this area. A comprehensive review by Sahajwalla and his colleagues published in July found that, to date, only a handful of approved drugs carry meaningful label information regarding obesity, such as specific dose adjustment (Clin. Pharmacol. Ther. 90, 77–89, 2011).

“Unless a specific drug is studied in obese patients during drug development, it's very difficult to extrapolate not only pharmacokinetics but also efficacy and safety information from normal-weight individuals to obese patients,” Sahajwalla says. “The main hurdle is lack of sufficient number of patients with varying degree of obesity in clinical trials.”

It's not that they're excluded. The FDA, for instance, encourages pharmaceutical companies to enroll obese subjects to collect data for dosing recommendations, says Sahajwalla. He's hopeful that as the scientific community continues to shed light on the need for actively including this population in trials, drugmakers will respond.

There are various efforts already underway to learn more. Earlier this year, for instance, Italian scientists proposed a systematic approach to dosing recommendations for anesthesia medications (Best Pract. Res. Clin. Anaesthesiol. 25, 27–36, 2011). And another group of Italian clinicians is currently conducting a three-year study looking at the changes in drug metabolism and pharmacokinetics in patients with morbid obesity after bariatric surgery.

In Cook's case, the lack of information prompted him and his colleagues to conduct their own study. They administered a single 750-milligram intravenous dose of levofloxacin to obese individuals who were hospitalized as well as those who were otherwise healthy. Their findings, published this summer, revealed that although peak concentrations of the antibiotic in both groups were comparable to that in normal-weight individuals, the elimination of the drug from the body was accelerated in the nonhospitalized obese arm (Antimicrob. Agents Chemother. 55, 3240–3243, 2011). The findings are medically relevant, Cook notes, because faster clearance of the antibiotic might make those patients more vulnerable to infection. “It's concerning,” he says, “because our data suggested that drug exposure would be almost half what it would be in a normal-weight individual, which might lead to more failures in obese patients.”

The study may have answered Cook's original question, but it also highlights how much remains unknown: “The more that we learn about how drugs behave in obese individuals,” he says, “the more we find that one size doesn't necessarily fit all.”