Pharmacokinetic and pharmacodynamic profiling of G-ABCD in rat model of invasive candidiasis.
J Glob Antimicrob Resist. 2020 Sep 02;:
Authors: Qi H, Li X, Chen Y, Zhang X, Yang M, Li C, Feng H, Zhang J, Li C
OBJECTIVES: We reported the pharmacokinetic/pharmacodynamic (PK/PD) targets of the biosimilar product of ABCD (G-ABCD) against Candida albicans (MIC 1-2 μg/mL) in a rat model of invasive candidiasis in order to facilitate its precision administration.
METHODS: Single-dose plasma PK of G-ABCD was studied in an invasive candidiasis rat model at dose level of 0.0625 to 10 mg/kg following intravenous administration. Amphotericin B concentrations were determined and based on those Amphotericin B concentrations in plasma, PK parameters were calculated. Efficacy of G-ABCD was evaluated after single administration by the log reduction of CFU count in kidney, liver, spleen and lung. The relationship between G-ABCD PK/PD index and log reduction of CFU count in kidneys were calculated and reported.
RESULTS: After intravenous administration of G-ABCD at dosage from 0.0625 to 10 mg/kg to rat, the maximum plasma concentration (Cmax) was 0.05-0.82 mg/L, area under the concentration-time curve from 0 to 24 h (AUC0-24) was 0.50-5.29 mg*h/L. G-ABCD showed potent antifungal activity against C. albicans C-13 with a maximum log reduction of 2.1 in kidney CFU count. The mean AUC0-24/MIC target of G-ABCD against C. albicans was 0.97 for stasis, 1.40 for 1-log kill, and 3.34 for 2-log kill, and the mean Cmax/MIC target was 0.063 for stasis, 0.097 for 1-log kill and 0.348 for 2-log kill.
CONCLUSION: Antifungal effect of G-ABCD was potent and correlated with AUC0-24/MIC and Cmax/MIC in this rat model of invasive candidiasis. Results in this study provided data for optimizing G-ABCD dosing regimen and breakpoints for antifungals.
PMID: 32890838 [PubMed - as supplied by publisher]