Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats
Abstract
:1. Introduction
2. Results and Discussion
2.1. Method Development
2.2. Method Validation
Concentration (ng/mL) | Intra-day R.S.D. (%) | Inter-day R.S.D. (%) | Accuracy R.E. (%) | Recovery (%) | |
---|---|---|---|---|---|
plasma | 10 | 9.5 | 9.2 | 6.6 | 95.6 |
100 | 6.8 | 8.4 | −5.5 | 96.8 | |
800 | 7.6 | 6.5 | 8.7 | 92.4 | |
tissue homogenate | 10 | 6.9 | 7.7 | −8.9 | 99.3 |
100 | 8.7 | 9.4 | 7.1 | 91.1 | |
800 | 8.6 | 9.5 | 5.5 | 93.1 |
2.3. Method Application
2.3.1. Pharmacokinetic Study
Stability | Added C (ng/mL) | Found C (ng/mL) | Accuracy R.E. (%) | |
---|---|---|---|---|
plasma | 48 h at room temperature | 10 | 9.1 | −9.0 |
100 | 95.7 | −4.3 | ||
800 | 789.4 | −1.3 | ||
1 month at −20 °C | 10 | 9.6 | −4.0 | |
100 | 96.2 | −3.8 | ||
800 | 814.2 | 1.8 | ||
three freeze-thaw cycles | 10 | 10.4 | 4.0 | |
100 | 94.2 | −5.8 | ||
800 | 759.1 | −5.1 | ||
tissue homogenate | 48 h at room temperature | 10 | 10.3 | 3.0 |
100 | 92.3 | −7.7 | ||
800 | 745.5 | −6.8 | ||
1 month at −20 °C | 10 | 9.2 | −8.0 | |
100 | 93.2 | −6.8 | ||
800 | 736.6 | −7.9 | ||
three freeze–thaw cycles | 10 | 9.4 | −6.0 | |
100 | 105.4 | 5.4 | ||
800 | 857.3 | 7.2 |
Parameter | Unit | Conventional Rats | HCC Model Rats |
---|---|---|---|
AUC(0-t) | µg·h/L | 236.8 ± 62.8 | 2006.0 ± 334.1 * |
AUC(0-∞) | µg·h/L | 263.4 ± 76.2 | 2251.9 ± 386.0 * |
MRT(0-t) | h | 1.21 ± 0.13 | 2.47 ± 0.32 * |
MRT(0-∞) | h | 1.68 ± 0.39 | 3.62 ± 1.11 * |
T1/2z | h | 1.25 ± 0.49 | 2.89 ± 1.78 * |
Tmax | h | 0.29 ± 0.10 | 1.00 ± 0.45 * |
Cmax | µg/L | 314.7 ± 82.0 | 713.4 ± 129.3 * |
CLz/F | L/h/kg | 80.8 ± 20.8 | 9.13 ± 1.75 * |
Vz/F | L/kg | 147.7 ± 78.0 | 37.2 ± 21.2 * |
2.3.2. Tissue Distribution Study
Plasma or Tissues | Fold Increase | ||
---|---|---|---|
0.5 h | 1.0 h | 3.0 h | |
plasma | 4.83 | 6.95 | 13.36 |
heart | 2.91 | 3.37 | 2.23 |
liver | 4.26 | 4.30 | 5.10 |
spleen | 4.63 | 4.26 | 2.31 |
lung | 1.83 | 1.82 | 1.65 |
kidney | 4.18 | 4.19 | 3.05 |
brain | 1.48 | 1.56 | 1.05 |
testis | 13.89 | 7.90 | 3.38 |
muscle | 0.94 | 1.09 | 1.30 |
fat | 5.95 | 3.96 | 4.46 |
stomach | 0.95 | 0.95 | 0.88 |
small intestine | 0.84 | 0.88 | 0.93 |
rectum | 0.97 | 1.06 | 0.93 |
3. Experimental
3.1. Materials, Reagents and Animals
3.2. Instrumentation and Conditions
3.3. Standard Solution and Quality Control Samples
3.4. Sample Preparation
3.5. Method Validation
3.6. Application to Pharmacokinetics and Tissue Distributions
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Peng, Y.; Ding, Y. Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats. Molecules 2015, 20, 4225-4237. https://doi.org/10.3390/molecules20034225
Peng Y, Ding Y. Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats. Molecules. 2015; 20(3):4225-4237. https://doi.org/10.3390/molecules20034225
Chicago/Turabian StylePeng, Yunru, and Yongfang Ding. 2015. "Pharmacokinetics and Tissue Distribution Study of Caudatin in Normal and Diethylnitrosamine-Induced Hepatocellular Carcinoma Model Rats" Molecules 20, no. 3: 4225-4237. https://doi.org/10.3390/molecules20034225