An Adaptive Biosystems Engineering Approach towards Modeling the Soluble-to-Insoluble Phase Transition of Clofazimine.

ABSTRACT: Clofazimine (CFZ) is a weakly basic, small-molecule antibiotic used for the treatment of mycobacterial infections including leprosy and multidrug-resistant tuberculosis. Upon prolonged oral administration, CFZ precipitates and accumulates within macrophages throughout the host. To model the pharmacokinetics of CFZ, the volume of distribution (Vd) was considered as a varying parameter that increases with continuous drug loading. Fitting the time-dependent change in drug mass and concentration data obtained from CFZ-treated mice, we performed a quantitative analysis of the systemic disposition of the drug over a 20-week treatment period. The pharmacokinetics data were fitted using various classical compartmental models sampling serum and spleen concentration data into separate matrices. The

SUBMITTER: Willmer AR 

PROVIDER: S-EPMC8779763 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature