Effects of Verapamil and Diltiazem on the Pharmacokinetics and Pharmacodynamics of Rivaroxaban
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Animal Study
2.3. Rivaroxaban Plasma Concentrations Measured by LC-MS/MS
2.4. Measurement of Prothrombin Time
2.5. Model Independent Data Analysis
2.6. Model Dependent Data Analysis
2.7. Statistical Analysis
3. Results and Discussion
3.1. Pharmacokinetics of Rivaroxaban in the Presence of Verapamil or Diltiazem
3.2. Prothrombin Time Following Oral Administration of Rivaroxaban in the Presence of Verapamil or Diltiazem
3.3. PK/PD Modeling
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameter | Rivaroxaban | Rivaroxaban + Verapamil | Rivaroxaban + Diltiazem |
---|---|---|---|
Cmax(ng/mL) | 373 (3) | 1079 (39) ** | 532 (31) * |
Tmax (h) | 2.8 (111) | 4.0 (63) | 1.6 (44) |
AUCinf (ng/mL) | 2699 (25) | 7606 (30) *** | 2915 (27) |
CL/F (mL/h/kg) | 774 (22) | 286 (35) *** | 723 (24) |
Parameter | Rivaroxaban | Rivaroxaban + Verapamil | Rivaroxaban + Diltiazem |
---|---|---|---|
Emax(%) | 30 (11) | 75 (14) * | 40 (7) |
AUEC(%∙h) | 188 (9) | 491 (10) * | 247 (14) |
Parameter | Rivaroxaban | Rivaroxaban + Verapamil |
---|---|---|
ka (h−1) | 0.63 (22) | 1.02 (19) ** |
V/F (mL/kg) | 960 (37) | 369 (37) ** |
ke (h−1) | 0.85 (27) | 0.80 (19) |
f (fraction) | 0.61 (30) | 0.61 (14) |
ttransit (h) | 6.37 (21) | 4.55 (15) * |
Slope (%·mL/ng) | 0.08 (44) | 0.08 (24) |
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Kim, M.; Son, H.; Noh, K.; Kim, E.; Shin, B.S.; Kang, W. Effects of Verapamil and Diltiazem on the Pharmacokinetics and Pharmacodynamics of Rivaroxaban. Pharmaceutics 2019, 11, 133. https://doi.org/10.3390/pharmaceutics11030133
Kim M, Son H, Noh K, Kim E, Shin BS, Kang W. Effects of Verapamil and Diltiazem on the Pharmacokinetics and Pharmacodynamics of Rivaroxaban. Pharmaceutics. 2019; 11(3):133. https://doi.org/10.3390/pharmaceutics11030133
Chicago/Turabian StyleKim, Minsoo, Heebin Son, Keumhan Noh, Eunyoung Kim, Beom Soo Shin, and Wonku Kang. 2019. "Effects of Verapamil and Diltiazem on the Pharmacokinetics and Pharmacodynamics of Rivaroxaban" Pharmaceutics 11, no. 3: 133. https://doi.org/10.3390/pharmaceutics11030133
APA StyleKim, M., Son, H., Noh, K., Kim, E., Shin, B. S., & Kang, W. (2019). Effects of Verapamil and Diltiazem on the Pharmacokinetics and Pharmacodynamics of Rivaroxaban. Pharmaceutics, 11(3), 133. https://doi.org/10.3390/pharmaceutics11030133