Evaluating posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults: A pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation

Abstract The objective of this study was to evaluate the efficacy of various posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults. Monte Carlo simulations (MCSs) were conducted using pharmacokinetic (PK) parameters and pharmacodynamics (PD) data to determine the probabilities of target attainment (PTA) and cumulative fractions of response (CFR) in terms of area under the concentration curve/minimum inhibition concentration targets of posaconazole. According to the results of the PTAs, currently clinical recommended dosing regimens of the delayed-release tablet and intravenous solution were appropriate in the prophylaxis against Aspergillus spp. with MICs ≤ 0.125 μg/mL. However, only high-dose regimens of the delayed-release tablet could achieve target PTAs in the treatment against Aspergillus spp. at an MIC of 0.125 μg/mL. Furthermore, CFR was calculated for each dosing regimen. For the oral suspension, none of the stimulating dosing regimens was effective against Aspergillus spp. For the delayed-release tablet and intravenous solution, the recommended dosing regimens were effective for the prophylaxis of invasive fungal infections by four Aspergillus spp. (Aspergillus. flavus, Aspergillus. fumigatus, Aspergillus. nidulans and Aspergillus. terreus). However, these recommended dosing regimens were only effective for the treatment of Aspergillus. terreus infection. Therefore, the high-dose regimen (200 mg p.o. q12h) of the delayed-release tablet should be recommended to attain optimal therapeutic efficacy against four Aspergillus spp. (Aspergillus. flavus, Aspergillus. fumigatus, Aspergillus. nidulans and Aspergillus. terreus). These PK/PD-based simulations rationalize and optimize the dosing regimens of the different posaconazole formulations against Aspergillus spp. in adults.