Resumo

INTRODUCTION: Infections associated with Candida include a broad spectrum of superficial and invasive disease, affecting patients exposed to a variety of risk factors, in particular the use of intravascular catheters, treatment with antineoplastic drugs and infection with HIV. Nowadays, the treatments of invasive candidiasis involve the use of Micafungin, a drug that belongs to a new class of antifungal agents named echinocandins. The objective of this work was to develop a PK/PD model to describe the fungicide effect of micafungin against C. Parapsilosis and C. tropicalis using an in vitro model of infection. Through the parameters determined by modeling is possible to predict outcomes to different dosing regimens considering the drug’s patients exposure and the killing effect. MATERIALS AND METHODS: The MIC was determined for both species using CLSI M27-A3 guideline. The in vitro model of infection was defined as one-compartment model, where total plasma concentrations of micafungin achieved in patients after administration of 25, 50, 75 or 150 mg by continuous infusion for 1h were simulated. The drug’s effect against Candida species were evaluated by counting the number of colony-forming unit (CFU), an estimate of viable fungal in the system after drug exposure for two hours up to fourteen hours. The sigmoid Emax model was used to describe the data using the software Scientist ® v.2.01. RESULTS AND DISCUSSION: The C. parapsilosis and C.tropicalis MICs were 1.00 μg/mL and 0.25 μg/mL, respectively, indicating the potent activity of micafungin against the yeasts tested. The mean PK/PD parameters obtained for C. parapsilosis after modeling were EC50 (concentration required for half of maximum effect) of 1.40 ± 0.04 μg/mL and kmax (maximum fungicide effect) of 1.71 ± 0.17 h-1; for C. tropicalis the mean value of EC50 was 3.31 ± 0.61 μg/ml and kmax 1.22 ± 0.11 h-1. The mean values of kmax determined for both species were comparable which means the similar drug effect against both Candida tested; however the EC50 was higher to C. tropicalis, showing that this specie could need higher doses to be eradicated from the infection. CONCLUSION: The PK/PD model was able to describe the killing curves versus time and the parameters determined can be used to predict different dosing regimens for micafungin against non-albicans species. ACKNOWLEADGMENTS: FAPERGS process # 111656-1.