Sotorasib exhibits pH-dependent solubility, making it susceptible to altered exposures when coadministered with acid-reducing agents (ARAs). Several clinical studies were conducted to investigate the impact of ARAs on sotorasib pharmacokinetics under different clinically relevant scenarios and to identify potential mitigation strategies. Upon coadministration of 960 mg of sotorasib and 40 mg of omeprazole under fasted conditions, sotorasib area under the concentration-time curve (AUC) and maximum observed plasma concentration (C) decreased approximately 42% and 57%, respectively.
View Article and Find Full Text PDFTBI-223, a novel oxazolidinone for tuberculosis, is designed to provide improved efficacy and safety compared to linezolid in combination with bedaquiline and pretomanid (BPaL). We aim to optimize the dosing of TBI-223 within the BPaL regimen for enhanced therapeutic outcomes. TBI-223 is investigated in preclinical monotherapy, multidrug therapy, and lesion penetration experiments to describe its efficacy and safety versus linezolid.
View Article and Find Full Text PDFThe tidal occurrence of larval fishes was investigated in the permanently open Kowie Estuary on the warm-temperate coast of South Africa. Larval fishes were sampled in the mouth region using two drifting light traps deployed on the ebb and flood tides every second night for two consecutive 14-day periods, coinciding with the dark moon phase. A total of 553 larval fishes were caught, representing nine families and 26 species, of which Blenniidae and Clupeidae dominated.
View Article and Find Full Text PDFParasites have deleterious effects on their hosts, often resulting in altered host behavior or increased energy expenditure. When organisms are exposed to suboptimal environments, parasite loading may increase. Microbialite pools along the warm temperate South African coastline have been hypothesized as refugia for Epaulette gobies (Coryogalops sordidus, Gobiidae) when they are outside of their previously known subtropical distribution.
View Article and Find Full Text PDF