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

The predicted ADMET properties of XKB, midazolam, ketoconazole, and probucol are shown in Table 6 . The aqueous solubility value (log [molar solubility]) of XKB was between -6.0 and -4.0. XKB showed a moderate ability to penetrate the blood-brain barrier and a good intestinal absorption profile. All properties and optimal prediction space components of XKB were within the expected ranges with regard to the CYP2D6 ligand, hepatotoxicity, and plasma protein binding level. Midazolam and ketoconazole showed similar ADMET profiles to XKB, except for hepatotoxicity. ADMET Predictor showed that the optimal prediction space PC25 values for midazolam and optimal prediction space PC30 values for ketoconazole were out of range, suggesting that both compounds might be hepatotoxic (Table 6 ). Probucol had very low aqueous solubility and very low intestinal absorption, which are in agreement with the data reported for this drug ( Table 6 ). The logP value for probucol is 10.91, 38 and its oral bioavailability is only about 10%, but can be improved using nanotechnology. [39] [40] [41] validation of HPLC method for determination of midazolam and 1′-OH-MDZ in rat plasma