Abstract
Micafungin is widely used for invasive candidiasis, especially in critically ill patients and those with cancer, and for empirical antifungal therapy in patients with neutropenic fever. This is the first study to investigate the pharmacokinetics and disposition parameters of micafungin in patients with cancer. In this observational pharmacokinetic study, blood samples were collected and analyzed using high-performance liquid chromatography. Pharmacokinetic parameters were estimated using Monolix 4.4 software. The plasma micafungin concentrations were measured in a total of 133 samples from 19 patients. In the final two-compartment model with linear elimination, the estimated micafungin clearance (CL) was significantly higher in patients with cancer than in those without cancer (1.2 vs. 0.6 L/h, p = 0.012), whereas other parameters did not significantly differ between the two groups. Aspartate and alanine transaminases and body weight significantly influenced micafungin CL in patients, with and without cancer. Overall, the probability of target attainment increased with increasing doses and decreased with higher MICs in both groups. In simulations, the patients without cancer achieved higher pharmacokinetic/pharmacodynamic targets with a 90% probability for all simulated doses, compared to the patients with cancer. Micafungin demonstrated dose-proportional linear pharmacokinetics in both the patients with and those without cancer. The estimated micafungin CL was significantly higher in patients with cancer, suggesting a need for increased dosage, especially for Candida spp. with high MICs, in these patients. Further studies should assess the efficacy and optimum dosage of micafungin for the treatment and prevention of febrile neutropenia (FN) in patients with cancer.
Highlights
Neutropenia is a common, serious complication of myelosuppressive chemotherapy and a leading cause of infection-related morbidity and mortality in patients with cancer [1]
Fungal infections are prevalent in highrisk patients with neutropenic fever, and patients with prolonged and severe neutropenia are at higher risk of candidemia and invasive fungal infections
We investigated the pharmacokinetics of micafungin in patients with cancer compared to those without cancer
Summary
Neutropenia is a common, serious complication of myelosuppressive chemotherapy and a leading cause of infection-related morbidity and mortality in patients with cancer [1]. Candida albicans is the most prevalent yeast pathogen responsible for fungal infections in neutropenic patients with cancer. Released clinical practice guidelines recommend the use of echinocandins, including anidulafungin, micafungin, and caspofungin, as first-line antifungals for the primary and secondary prevention of FN in high-risk patients [13–15]. These antifungals are recommended as empirical antifungal therapy in patients with persistent FN [13–15]. Compared to other systemic antifungals, the advantages of echinocandins include a relatively better toxicity profile and less potential for drug-drug interactions [16]. We investigated inter-individual variability and assessed the probability of achieving PK/PD targets with current dosing strategies in this patient population, with the overarching aim of providing the basis for establishing an effective and safe micafungin dose regimen for patients with cancer
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