BOSTON—New data presented at the 50th Interscience Conference on Anti - microbial Agents and Chemo therapy (ICAAC) suggest that standard doses of antibiotics may not be the right dose for obese individuals and that obese patients may need higher doses for some agents. In addition, the researchers said that more studies are needed to determine correct dosages of drugs for the obese.
“Stop using the ideal body weight equations and its derivative (adjusted body weight). Consider using lean body weight–2005 (LBW2005) when estimating kidney function in the morbidly obese subject. Oncology pharmacists need to study the role of LBW2005 for dosing cancer chemotherapy agents as a potential surrogate of body surface area. This is important because body surface area is not estimated differently for men and women of equal height and weight. LBW2005 gives you estimates by sex, which is important due to known physiological differences,” said Manjunath Pai, PharmD, an associate professor at the Albany College of Pharmacy and Health Sciences, New York.
He said oncology pharmacists need to be fully aware of the LBW2005 equation. Pharmacists have historically used the Devine formula, which was based on ideal body weight. Pai said that the Devine formula was not derived on solid scientific grounds. Along with Paloucek, he has published a paper outlining the history of this formula (Ann Pharmacother. 2000; 34:1066-1069).
“The goal of calculating ideal body weight was to get an estimate of lean body weight. It is important to recognize that many equations have been generated over time to estimate lean body weight. All these previous equations are limited in that they are linear equations. That is to say that the estimate of lean body weight increases in proportion to total body weight as one goes from 50 kg to say 250 kg,” Pai explained.
The LBW2005 equation is superior to previous equations because it is nonlinear and gives better estimates of lean body weight according to Pai. Simply put, the estimate of an individual subject’s lean body weight using LBW2005 increases by approximately twofold even though their total body weight increases by fourfold (50-200 kg). Pai applied this equation and demonstrated its superiority when dosing aminoglycosides, ertapenem, daptomycin, and voriconazole. Several investigators have demonstrated this for agents other than antibiotics as well.
At the ICAA meeting, Pai presented the findings from his current study that showed estimated lean body weight was more useful than measured total body weight to decrease the pharmacokinetics of the drug ertapenem in normal weight and obese individuals. Lean body weight represents the “nonfat” or “fat-free weight” of a patient based on his or her sex. This information may be helpful because it could be used to estimate the dose of drugs that are similar to ertapenem.
The researchers found that a higher dose of ertapenem may be necessary in obese patients compared with nonobese patients. Ertapenem is commonly given before surgery to prevent infections.
When most drugs now on the market were approved for commercial use, little information was available on dosing obese patients. For antibiotics, using a dose that is too low could lead to treatment failure and increase bacterial resistance, resulting in superinfections. Pai said that an antimicrobial dose that is too high could also lead to avoidable side effects. He and his colleagues noted that improving outcomes in obese patients with infections by using the appropriate antibiotic dose could reduce morbidity and mortality, and result in significant cost savings.