Abstract
The objective of this study was to investigate the probability of target attainment of various posaconazole dosing regimens against Mucorales species in patients with mucormycosis. According to pharmacokinetic/pharmacodynamic parameters of posaconazole in adults, the dosage regimen of posaconazole for mucormycosis included 50, 100, 200 and 400 mg orally q12h. Monte Carlo Simulation analysed the published parameters of pharmacokinetics and the MIC values of mucormycosis in Mucorales species. The results showed that posaconazole did not affect Rhizopus arrhizus and Mucor sp. The optimal dosage of posaconazole for Rhizopus microsporus and Rhizomucor pusillus was 400 mg orally q12h and the best dosage regimen for Lichtheimia corymbifera was 200 mg orally q12h. The antifungal activity of posaconazole against mucormycosis was different, and the dosage regimen needs to adjust according to fungal species.
Highlights
Mucormycosis was a fatal fungal infection caused by Mucorales, which was a subdivision of mucoromycotina
The results Monte Carlo simulation of four different administration dosage of posaconazole showed that the patients with mucormycosis meet the requirement of probability of target attainment (PTA) ≥ 90% in the dosage of 400 mg orally q12h
The results of dosage of posaconazole 100 mg showed that PTA ≥ 90% at the highest Minimum Inhibition Concentration (MIC) values for Lichtheimia corymbifera, Rhizopus arrhizus, Rhizopus microsporus, Mucor sp., and Rhizomucor pusillus were 0.125 μg/mL, 0.25 μg/mL, 0.25 μg/mL, 0.125 μg/mL, 0.25 μg/mL, respectively
Summary
Mucormycosis was a fatal fungal infection caused by Mucorales, which was a subdivision of mucoromycotina. Mucormycosis was the second common fungal infection in hematological malignancies and organ transplantation [1]. It has been reported more and more in patients with diabetes or ketoacidosis and after trauma in patients with normal immune function, even in healthy. There are limited reports on the treatment of mucormycosis by the dose of posaconazole, with the maximum daily dose of 800 mg [9]. In this study, the administration scheme of posaconazole for the treatment of mucormycosis needs to be optimized, and the optimal drug administration scheme optimised to provide a basis for clinical application
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