TITLE:
Analysis of Pharmacokinetic/Pharmacodynamic Parameters and Dosage Regimen of Posaconazole against Candida spp. and Aspergillus spp. Using Monte Carlo Simulation
AUTHORS:
Ying Wang, Jingyi Zhao, Junhui Hu, Xinhong Zhao, Yinhui Yao
KEYWORDS:
Posaconazole, Monte Carlo Simulation, Candida spp., Aspergillus spp., Pharmacokinetics/Pharmacodynamics
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.11 No.1,
January
17,
2020
ABSTRACT: Invasive fungal infections (IFI)
have recently become increasingly more prevalent, resulting in an increased
risk of morbidity and mortality. Both Candida spp. and Aspergillus spp. are major
causes of IFI. In this study, we aimed to evaluate the cumulative fraction of
response of various dosage regimens of posaconazole against nine Candida spp. and six Aspergillus spp. in both children and
adults. Monte Carlo simulation (MCS) was performed to optimize selection
of posaconazole dosage regimens. For children, a dosage regimen of 120 mg/m2 posaconazole tid was sufficient to treat fungal infections caused by all six Aspergillus spp. and six of the nine Candida spp. (but was not effective
against C. glabrata, C. guilliermondii and C. krusei). In contrast,
a 400 mg dosage regimen of posaconazole bid achieved the target
pharmacokinetic/pharmacodynamics (PK/PD) parameters against all six Aspergillus spp. and eight of the nine Candida spp. (but was not effective
against C. glabrata) in the adults. Dosage regimens of 50 mg bid, 100 mg bid,
or 200 mg bid were not effective. Posaconazole dosage regimens are likely to
achieve their desired PK/PD targets against Candida spp. and Aspergillus spp. in both
children and adults.