A Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-Hepatocellular Carcinoma Compound 4-N-Carbobenzoxy-gemcitabine (Cbz-dFdC)
Abstract
:1. Introduction
2. Results
2.1. Plasma Pharmacokinetics In Vivo
2.2. Tissue Distribution
2.3. Enzymatic Kinetics In Vitro
2.4. Cell Efficacy and Unptake
2.5. Antitumor Efficacy In Vivo
3. Discussion
4. Materials and Methods
4.1. Materials and Equipment
4.2. Animals
4.3. The Synthesis of Cbz-dFdC
4.4. Pharmacokinetics In Vivo
4.5. Tissue Distribution
4.6. Enzymatic Kinetics In Vitro
4.7. Antitumor Efficacy and Uptake In Vitro
4.8. Antitumor Efficacy In Vivo
4.9. Data Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: All Samples are available from the authors. |
Parameters | Cbz-dFdC (i.g. 22 mg/kg) | dFdC (i.v. 15 mg/kg) | |
---|---|---|---|
Cbz-dFdC | dFdC | dFdC | |
t1/2 (h) | 9.91 ± 1.87 | 10.43 ± 0.91 | 10.56 ± 1.86 |
AUC0–∞ (ng·h/mL) | 2691.3 ± 456.8 | 27,498.0 ± 5653.3 | 22,685 ± 4136.2 |
Tmax (h) | 2.00 ± 0.00 | 4.00 ± 0.00 | 0.083 ± 0.00 |
Cmax (ng/mL) | 451.1 ± 106.7 | 1656.3 ± 431.5 | 14,145 ± 4115 |
Parameters | Disappearance of Cbz-dFdC | Appearance of dFdC | ||||
---|---|---|---|---|---|---|
Vmax (nmol/min/mg pro) | Km (μM) | Clint (mL/min/mg) | Vmax (nmol/min/mg pro) | Km (μM) | Clint (mL/min/mg) | |
Rat Blood | 341.1 | 69.8 | 4.89 | 178.5 | 73.2 | 2.44 |
Rat Plasma | 486.2 | 90.3 | 5.38 | 230.4 | 101.2 | 2.28 |
Rat Liver Homogenate | 411.6 | 189.6 | 2.17 | 86.8 | 96.4 | 0.90 |
Rat Liver S9 | 169.6 | 96.3 | 1.76 | 49.5 | 41.2 | 1.20 |
Rat Kidney Homogenate | 162.7 | 147.5 | 1.10 | 44.3 | 48.9 | 0.91 |
Rat Kidney S9 | 206.5 | 269.3 | 0.77 | 50.2 | 78.7 | 0.64 |
Human Liver S9 | 1491.3 | 107.8 | 13.83 | 480.6 | 65.7 | 7.32 |
Human CES1 Recombinase | 18,802.3 | 258.6 | 72.71 | 3910.4 | 107.2 | 36.48 |
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Sun, Y.; Wang, J.; Hao, K. A Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-Hepatocellular Carcinoma Compound 4-N-Carbobenzoxy-gemcitabine (Cbz-dFdC). Molecules 2020, 25, 2218. https://doi.org/10.3390/molecules25092218
Sun Y, Wang J, Hao K. A Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-Hepatocellular Carcinoma Compound 4-N-Carbobenzoxy-gemcitabine (Cbz-dFdC). Molecules. 2020; 25(9):2218. https://doi.org/10.3390/molecules25092218
Chicago/Turabian StyleSun, Yilin, Jiankun Wang, and Kun Hao. 2020. "A Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-Hepatocellular Carcinoma Compound 4-N-Carbobenzoxy-gemcitabine (Cbz-dFdC)" Molecules 25, no. 9: 2218. https://doi.org/10.3390/molecules25092218