Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat Cholestatic Liver Injury
Abstract
:1. Introduction
2. Results
2.1. HPLC Analysis
2.1.1. HPLC Method Validation
2.1.2. Standard Curve
2.1.3. Precision and Accuracy
2.1.4. Stability
2.1.5. Extraction Recovery
2.2. PK Research
2.3. PK-PD Modelling
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Drugs and Reagents
5.2. Animals
5.3. Instruments
5.4. Liquid Chromatography
5.5. Standard Solution and Sample Preparation
5.6. PK and PD Research
5.7. Blood Biochemical Determinations
5.8. Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Sample Availability: Samples of the compound (RA) is available from the authors. |
Concentration/µg·mL−1 | RSD (%) | ||
---|---|---|---|
Inter-Day Precision | Intra-Day Precision | Accuracy | |
35 | 1.44 | 3.84 | 2.89 |
48 | 2.34 | 4.65 | 2.58 |
70 | 1.44 | 3.85 | 1.37 |
Concentration/µg·mL−1 | RSD% | ||
---|---|---|---|
6 h at 25 °C | 6 h at 4 °C | 7 d at −80 °C | |
35 | 1.44 | 2.05 | 5.72 |
48 | 2.34 | 2.86 | 5.98 |
70 | 1.44 | 2.32 | 5.31 |
Concentration/μg·mL−1 | The Recovery | RSD/% | The Absolute Recovery | RSD/% |
---|---|---|---|---|
35 | 96.7 ± 3.72 | 3.84 | 91.48 ± 1.00 | 1.09 |
48 | 94.54 ± 1.61 | 1.71 | 95.82 ± 1.71 | 1.78 |
70 | 89.98 ± 1.92 | 2.14 | 88.97 ± 2.80 | 3.15 |
Pharmacokinetic Parameters | Unit | Normal Group | Model Group |
---|---|---|---|
AUC | mg·h/mL | 20.500 ± 1.199 ** | 23.984 ± 0.678 |
K01_HL | h | 0.181 ± 0.061 ** | 0.303 ± 0.092 |
K10_HL | h | 4.930 ± 0.419 | 4.799 ± 0.264 |
CL_F | L/h/kg | 4.876 ± 0.285 ** | 4.169 ± 0.118 |
Tmax | h | 0.704 ± 0.120 | 0.988 ± 0.153 |
Cmax | mg/mL | 2.542 ± 0.054 ** | 2.876 ± 0.082 |
V_F | L/kg | 34.683 ± 1.433 | 28.867 ± 1.438 |
K01 | h−1 | 3.827 ± 1.283 | 2.291 ± 0.698 |
K10 | h−1 | 0.141 ± 0.012 | 0.144 ± 0.008 |
Parameter | Model Group | Blank Group | ||
---|---|---|---|---|
AST | ALT | AST | ALT | |
Imax | 6765.54 | 3660.634 | 855.64 | 338.667 |
IC50 | 14.369 | 7.460 | 12.640 | 12.702 |
E0 | 1175.756 | 978.187 | 309.569 | 129.138 |
Ke0 | 1.476 | 1.346 | 2.538 | 1.662 |
Parameter | Model Group | Blank Group | ||
---|---|---|---|---|
TBIL | TBA | TBIL | TBA | |
Emax | 20.279 | 46.028 | 84.572 | 96.36 |
EC50 | 3.410 | 4.589 | 4.769 | 6.235 |
E0 | 2.855 | 4.183 | 13.935 | 21.85 |
Gamma | 2.895 | 2.122 | 3.1445 | 2.283 |
Ke0 | 1.780 | 1.535 | 2.067 | 1.918 |
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Min, J.; Chen, H.; Gong, Z.; Liu, X.; Wu, T.; Li, W.; Fang, J.; Huang, T.; Zhang, Y.; Zhao, W.; et al. Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat Cholestatic Liver Injury. Molecules 2018, 23, 2287. https://doi.org/10.3390/molecules23092287
Min J, Chen H, Gong Z, Liu X, Wu T, Li W, Fang J, Huang T, Zhang Y, Zhao W, et al. Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat Cholestatic Liver Injury. Molecules. 2018; 23(9):2287. https://doi.org/10.3390/molecules23092287
Chicago/Turabian StyleMin, Jianbin, Hao Chen, Zipeng Gong, Xian Liu, Tian Wu, Weirong Li, Jiansong Fang, Tianlai Huang, Yingfeng Zhang, Wei Zhao, and et al. 2018. "Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat Cholestatic Liver Injury" Molecules 23, no. 9: 2287. https://doi.org/10.3390/molecules23092287
APA StyleMin, J., Chen, H., Gong, Z., Liu, X., Wu, T., Li, W., Fang, J., Huang, T., Zhang, Y., Zhao, W., Zhu, C., Wang, Q., Mi, S., & Wang, N. (2018). Pharmacokinetic and Pharmacodynamic Properties of Rosmarinic Acid in Rat Cholestatic Liver Injury. Molecules, 23(9), 2287. https://doi.org/10.3390/molecules23092287