Pharmacokinetic/pharmacodynamic study of posaconazole delayed-release tablet in a patient with coexisting invasive aspergillosis and mucormycosis

Abstract

Limited information exists regarding the optimal dose of posaconazole delayedrelease tablet for the treatment of invasive mold infection. Here, we report the case of a previously healthy 44-year-old Thai man who developed coexisting invasive pulmonary aspergillosis and mucormycosis following a car accident. He was treated with posaconazole delayed-release tablet. This report describes the pharmacokinetic/pharmacodynamic study, safety profile, and determination of the appropriate dosage of posaconazole delayed-release tablet in a patient with coexisting invasive aspergillosis and mucormycosis. Posaconazole exposure was analyzed by noncompartmental model. Ratio of area under the plasma concentration- time curve over the minimum inhibitory concentration (AUC/MIC) was applied to maximize the efficacy of posaconazole. The loading dose of 300 mg q 12 hrs was found to be potentially insufficient for achieving the AUC/MIC target for treatment of invasive mold infection with minimum inhibitory concentrations >0.01 mg/L. Early therapeutic drug monitoring to detect the drug concentration of posaconazole delayed-release tablet is necessary so that dosing adjustments can be made, as needed. In addition, a maintenance dose of either 400 or 300 mg once daily could achieve the AUC/MIC targets. These maintenance dosing regimens effectuated a successful clinical outcome with minimal adverse events.