Progress of triazole antifungal agent posaconazole in individualized therapy

Abstract

What is known and objective: Posaconazole is the second-generation triazole antifungal agent with widespread clinical application. Posaconazole exposure is influenced by various factors such as drug interactions, disease state and diet, resulting in a high interindividual variability in many patients and failure to ensure therapeutic efficacy. Therefore, it is necessary to conduct individualized therapy on posaconazole to ensure the efficacy and safety of treatment.Methods: Articles were identified through PubMed using the keywords such as "posaconazole," "therapeutic drug monitoring" and "Population pharmacokinetics" from 1 January 2001 to 30 April 2022. Results and discussion: In this paper, we review the individualized treatment studies of posaconazole from the three aspects of therapeutic drug monitoring, population pharmacokinetic study and Monte Carlo simulation to provide reference for in-depth individualized posaconazole dosing studies. What is new and conclusion: This review suggests that therapeutic drug monitoring should be performed in patients taking posaconazole to adjust the dosage and assess the efficacy and cost-effectiveness of posaconazole under different clinical conditions and different dosing regimens through Monte Carlo simulations. In the future, a more detailed delineation and comprehensive examination of posaconazole PPK for specific populations requires further study.

Novel Triazoles with Potent and Broad-Spectrum Antifungal Activity In Vitro and In Vivo

“… − A remarkable example of this is POS, whose long-tail structure (Figure D) enables it to treat FLC-resistant candidiasis, aspergillosis, and cryptococcosis. POS’s long side chain interacts with hydrophobic amino acids in its X-ray crystal structure with CYP51, , emphasizing the importance of hydrophobic forces in developing new azole drugs. , Although many molecules have been designed with a long chain for other purposes like dual-inhibiting, , only a few studies have directly aimed to develop rational side chains for improving the efficiency of new antifungal agents. , The discovery of more efficient candidates from such studies suggests the diverse potential interactions between the long hydrophobic pocket and different inhibitors.…”