Therapeutics and Clinical Risk Management (Apr 2019)
Pharmacokinetic/pharmacodynamic study of posaconazole delayed-release tablet in a patient with coexisting invasive aspergillosis and mucormycosis
Abstract
Pannee Leelawattanachai,1,2 Preecha Montakantikul,1 Wichit Nosoongnoen,1 Methee Chayakulkeeree31Division of Clinical Pharmacy, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 2Department of Pharmacy, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand; 3Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandAbstract: Limited information exists regarding the optimal dose of posaconazole delayed-release 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.Keywords: antifungal, treatment, therapeutic drug monitoring, AUC/MIC, invasive fungal infection, mixed infection
