Pharmacokinetics of anidulafungin in obese and normal-weight adults [PublishAheadOfPrint]

In 2025, approximately one out of five adults will be obese. Physiological changes associated with obesity have shown to influence the pharmacokinetics of drugs. Anidulafungin is frequently used in critically ill patients and to achieve optimal efficacy it is essential that its dose is appropriate for each patients' characteristics. We combined data from obese subjects with data from normal-weight subjects and determined an optimal dosing regimen for obese patients by population-PK modeling.

Twenty adults, of which twelve were normal-weight healthy subjects (median weight 67.7 kg; range: 61.5-93.6 kg) and eight morbidly obese subjects (median weight 149.7 kg; range: 124.1-166.5 kg) were included in the analysis. Subjects received a single dose of 100 mg anidulafungin IV in 90 minutes upon which blood samples were obtained. Monte Carlo simulations were performed to optimize dosing in obesity.

A three-compartment model and equal volumes of distribution described the data best. Total body weight was identified as descriptor for both clearance and volume of distribution but the effect of weight on these parameters was limited. Simulations showed that with the licensed 100 mg dose more than 97% of subjects with a weight above 140 kg will have an AUC_0-24 lower than 99 mg*h/L (reference of normal weight individuals).

We found that anidulafungin pharmacokinetics in obese and normal-weight subjects, weight influenced both clearance and volume of distribution implying a lower exposure to anidulafungin in (morbidly) obese individuals. Consequently, a 25% increase in loading and maintenance dose could be considered in patients weighing more than 140 kg.

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