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

Abstract

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.

Consensus guidelines for optimising antifungal drug delivery and monitoring to avoid toxicity and improve outcomes in patients with haematological malignancy and haemopoietic stem cell transplant recipients, 2021

“…[218][219][220][221] However, the application of target ratios derived from animal models to the clinical setting is ill-defined. 14,222,223 An AUC/MIC ratio of 200 has been suggested for infections involving Aspergillus spp. in clinical practice.…”

“…179 If posaconazole tablet dosing of 400 mg daily is subtherapeutic, consider twice-daily dosing rather than once-daily dosing due to probable saturation of absorption. 222 However, extreme caution should be taken when using twice-daily dosing for posaconazole tablets, and three times-daily dosing of posaconazole tablets should be avoided. There are case reports of wrong oral formulations of posaconazole being prescribed and/or dispensed, with one case resulting in death.…”