Pharmacokinetics and probability of target attainment for micafungin in normal-weight and morbidly obese adults

Objectives The rising pandemic of obesity means an increasing number of obese patients who require antimicrobial therapy for serious infections. Micafungin is an echinocandin drug frequently used as therapy or prophylaxis for fungal infections, predominantly with Candida species. In order to maximize the efficacy of micafungin in obese patients, the dose that corresponds to optimal exposure for each obese individual needs to be identified. Methods We performed a prospective study in 16 obese and 8 normal-weight healthy subjects with a weight ranging from 61.5-184kg (ClinicalTrials.gov Identifier: NCT03102658). A population pharmacokinetic model was developed and used to simulate several dosing regimens to evaluate the PTA for relevant MICs to define the optimal dose using the pharmacokinetic/pharmacodynamic target of an AUC/MIC ratio above 5000. Results Total body weight was found to be most predictive for CL and V. Simulations showed that a 100mg dose results in a PTA of >90% in patients weighing 125kg infected with a Candida species having an MIC of 0.016mg/L. The maintenance dose should be increased to 200mg in patients >125kg infected with a Candida species with an MIC of 0.016mg/L. For an MIC of 0.032mg/L, a 300mg maintenance dose is recommended above 125kg weight. Furthermore, we demonstrate that patients can benefit from a loading dose (i.e. twice the maintenance dose). Conclusions We present easy-to-use dose recommendations for obese patients, based on both weight and target MIC, that result in adequate exposure in patients with body weight up to 190kg.