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INTRODUCTION: Posaconazole was approved by the FDA for use as prophylaxis against invasive Aspergillus and Candida infections in immunocompromised patients. In spite of it, the dosing regimens of this drug is still defined by MIC and its relationship with PK exposure, by PK/PD indexes. In the present study is described the use of PK/PD modeling, an integrative and more predictive approach to improve dosing regimens in clinical practice, which has been rarely applied to antifungal agents. In this context, the aim of this study was to apply a PK/PD modeling for posaconazole, against C. tropicalis employing an in vitro model of infection. MATERIALS AND METHODS: A one-compartment in vitro model was used to simulate posaconazole plasma levels expected after oral administrations of 100, 200 and 400mg doses (q12h and q24h). The drug was added into the system to reach concentrations equivalent to the peak plasma levels expected after each dose and, by sequential dilution, the drug’s half-live of 24h was simulated. The antifungal effect was evaluated by determining the number of yeasts over time up to 24 h. RESULTS AND DISCUSSION: An Emax-model was used to model the dynamic effect as a function of time and fluctuating concentrations using Scientist® v 2.01 software. Posaconazole showed a fungistatic effect against C. tropicalis. The mean PK/PD parameters obtained by the modeling were: EC50 (concentration required for half of maximum effect) of 0,43 ± 0,09 μg/mL and kmáx (maximum fungistatic effect) of 0,81 ± 0,22 h^-1 for C.tropicalis. An interesting result of this study was the difference in kmáx obtained when the drug was administered in different regimens - once or twice a day (Dose (mg) / τ (h) - 100/24, 100/12, 200/24, 200/12 and 400/24, 400/12), respectively, where the following mean values were obtained: kmáx 0.61, 0.84, 0.83, 0.84, 0.78 and 0.98 h^-1, the comparison among the values, showed that they were slightly higher when the drug was taken twice daily, as to a single administration, which could serve as indication for the choice of this regimen. CONCLUSION: The PK/PD model tested adequately described posaconazole antifungal activity and can be used to compare and optimize drug regimens for this drug. ACKNOWLEADGMENTS: FAPERGS process (# 111656-1).