In silico-derived bedside formula for individualized micafungin dosing for obese patients in the age of deterministic...

There are 2.1 billion people worldwide who are overweight or obese. However, most current doses of drugs were derived for normal weight patients. For several drugs, the relationship between clearance and patient weight follows fractal geometry rules. Clearance directly determines the area under the concentration time curve (AUC) after i.v. infusion. For micafungin, AUC-to-minimum inhibitory concentration (AUC/MIC) ratios have a close deterministic relationship with efficacy in candidiasis; an AUC/MIC ≥3,000 is associated with 98% efficacy. We performed computer-aided clinical trial simulations of 100,000 patients with candidiasis to identify the lowest micafungin dose able to achieve AUC/MIC ≥3,000 in patients weighing up to 200 kg. We used the cumulative fraction of response to derive the formula "Dose (mg) = patient weight + 42" for use by the clinician at the bedside to individualize micafungin doses for overweight and obese patients. This paradigm for dose individualization could be used to optimize efficacy for many classes of anti-infective agents in obese patients.