Enantioselective in vitro ADME, absolute oral bioavailability and pharmacokinetics of (-)-lumefantrine and (+)-lumefantrine in mice.

Enantioselective in vitro ADME, absolute oral bioavailability and pharmacokinetics of (-)-lumefantrine and (+)-lumefantrine in mice.
Xenobiotica. 2020 Sep 15;:1-32
Authors: Babulal Gabani B, Dixit A, Kiran V, Bestha RM, Balaji N, Srinivas NR, Mullangi R
Abstract
Lumefantrine (LFN) is a chiral anti-malarial drug. Enantioselective in vitro attributes and absolute oral pharmacokinetics for (-)-LFN and (+)-LFN have been characterized in mice.No stereoselectivity was seen with either of the enantiomers when compared with rac-LFN in the executed in vitro studies (solubility, metabolic stability, protein binding, permeability and blood partitioning).Post intravenous or oral administration of rac-LFN, the AUC0-∞ and MRT of (+)-LFN was higher over (-)-LFN, which is reflected in higher clearance value for (-)-LFN.Following (-)-LFN intravenous administration to mice the key PK parameters were comparable to (-)-LFN from rac-LFN; however, post intravenous administration of (+)-LFN alone to mice, the AUC0-∞ was 1.3-fold higher than (+)-LFN from rac-LFN.Similarly, post oral administration of (-)-LFN to mice, both AUC0-∞ and Cmax were 1.3-fold higher than (-)-LFN from rac-LFN. On other hand, (+)-LFN showed 2.4-fold higher AUC0-∞ and 1.7-folder higher Cmax post oral administration over (+)-LFN from rac-LFN.
PMID: 32930648 [PubMed - as supplied by publisher]

Source: Xenobiotica - September 14, 2020 Category: Research Authors: Babulal Gabani B, Dixit A, Kiran V, Bestha RM, Balaji N, Srinivas NR, Mullangi R Tags: Xenobiotica Source Type: research