Non-clinical pharmacokinetics study in rat plasma, tissues and excreta of honokiol derivative HM475 by UPLC-Q-TOF-MS/MS

Comprehensive Stereoselectivity Assessment of Toxicokinetics, Tissue Distribution, Cytotoxicity, and Environmental Fate of Chiral Pesticide Propiconazole

“…The maximum plasma concentrations ( C max ) of trans (−)-2 R ,4 R -, trans (+)-2 S ,4 S -, cis (+)-2 R ,4 S -, and cis (−)-2 S ,4 R -PRO could achieve 4.86 ± 0.40, 3.84 ± 0.54, 10.15 ± 1.15, and 7.46 ± 1.26 μg/mL, respectively. Some studies had proved that the occurrence of second absorption peak could be associated with the reasons of enterohepatic circulation, different absorption mechanisms of drugs in the gastrointestinal tract, and higher plasma protein binding rate . Though the T max values (1.50 ± 0.00 h) of the four enantiomers were the same, the concentrations of trans (−)-2 R ,4 R - and cis (+)-2 R ,4 S -PRO in rat plasma were always higher than their antipodes from 0 to 24 h. The C max value of trans (−)-2 R ,4 R -PRO was 1.27 times higher than that of trans (+)-2 S ,4 S -PRO, and the area under the plasma drug concentration–time curve to infinity (AUC 0–∞ ) of trans (−)-2 R ,4 R -PRO was 1.19-fold higher than that of trans (+)-2 S ,4 S -PRO.…”

“…Some studies had proved that the occurrence of second absorption peak could be associated with the reasons of enterohepatic circulation, 34 different absorption mechanisms of drugs in the gastrointestinal tract, and higher plasma protein binding rate. 35 Though the T max values (1.50 ± 0.00 h) of the four enantiomers were the same, the concentrations of trans (−)-2R,4R-and cis (+)-2R,4S-PRO in rat plasma were always higher than their antipodes from 0 to 24 h. The C max value of trans (−)-2R,4R-PRO was 1.27 times higher than that of trans (+)-2S,4S-PRO, and the area under the plasma drug concentration−time curve to infinity (AUC 0−∞ ) of trans (−)-2R,4R-PRO was 1.19-fold higher than that of trans (+)-2S,4S-PRO. However, in terms of cisforms, the C max and AUC 0−∞ of cis (+)-2R,4S-PRO were 1.36 and 1.52 times higher than those of cis (−)-2S,4R-PRO, respectively.…”