Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study

Su, Junhui; Chang, Cui; Xiang, Qi; Zhou, Zhi-Wei; Luo, Rong; Yang, Lun; He, Zhi-Xu; Yang, Hongtu; Li, Jianan; Bei, Yu; Xu, Jinmei; Zhang, Minjing; Zhang, Qihao; Su, Zhijian; Huang, Yadong; Pang, Jiyan; Zhou, Shu-Feng

Following determination of their plasma concentrations, the PK parameters of midazolam and 1′-OH-MDZ were calculated by single-compartmental analysis using the PKSlover program (China Pharmaceutical University, Nanjing, People's Republic of China), 31, 32 which is a freely available menu-driven add-in program for Microsoft Excel written in Visual Basic for Applications for PK data analysis. The PK parameters calculated were the absorption rate constant (k a ), elimination rate constant (k e ), half-life of absorption (t 1/2ka ), half-life of elimination (t 1/2ke ), volume of distribution (V/F), body clearance (CL/F), maximum plasma concentration observed (C max ), time to reach C max (T max ), area under the plasma concentration-time curve (AUC 0-t ), AUC 0-inf , area under the first moment curve (AUMC), and mean residence time. The t 1/2ke was calculated using the formula t 1/2ke =0.693/ k e . The AUC was calculated using the trapezoidal rule. CL was calculated by the formula CL/F = dose/AUC. The V/F following oral administration was calculated using the V/F = CL/F/k e equation.