Key result
Ethambutol systemic clearance was proportional to body mass, resulting in a decreased area under the concentration-time curve for obese patients compared to leaner patients.
Why the study?
How does body mass affect ethambutol pharmacokinetics in adult volunteers?
How does body mass affect ethambutol pharmacokinetics in adult volunteers?
Ethambutol clearance increases with body mass, leading to reduced AUC in obese patients and suggesting a need for individualized dosing regimens.
May reduce ethambutol exposure in obese adults; hypothesis-generating for weight-based dosing trials.
We conducted a prospective study of 18 adult volunteers (male-to-female ratio of 1) whose body mass index fell into categories of <25, 25 to 40, or >40 kg/m(2), who received a single oral dose of 1,600 mg ethambutol. Only individuals with normal renal function were recruited. The minimum body mass (M) was 45.6 kg, the median was 90.8 kg, and the maximum weight was 160.4 kg. Ethambutol pharmacokinetics were best described by a two-compartment model. Inclusion of weight as a covariate dramatically improved the model, with a relative likelihood approaching infinity. The typical clearance was 42.6 liters/h. Ethambutol systemic clearance was proportional to (M/45.6)(3/4) and thus obeyed fractal geometry-based laws. This means that the area under the concentration-time curve (AUC) actually decreased for obese patients compared to that for leaner patients, reducing chances of concentration-dependent toxicity. On the other hand, such reduced AUCs could lead to therapy failure. Thus, new and individualized ethambutol dosing regimens need to be designed for obese and extremely obese patients.
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Hall et al. (2011) studied Obesity (n=18). Ethambutol vs. Leaner patients (BMI <25 kg/m2) was evaluated on Ethambutol pharmacokinetics (clearance and AUC). Ethambutol systemic clearance was proportional to body mass, resulting in a decreased area under the concentration-time curve for obese patients compared to leaner patients.
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