Pharmacokinetic Interactions Between Concomitantly Administered Phenytoin With Rivaroxaban

Reddy, Y. Karnakar; Reddy, Tummaluru Ramamohan

doi:10.25004/ijpsdr.2018.100507

Cited by 1 publication

(1 citation statement)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To the best of our knowledge, there were no studies conducted to investigate the effects of CBZ or PHT (CBZ/PHT) on both the pharmacokinetics (PK) and the pharmacodynamics (PD) of RIV. Only one study was reported the effects of PHT on the PK of RIV; however, no information regarding administered doses was reported [31]. Our study was, therefore, conducted to solve the lack of information.…”

Section: Introductionmentioning

confidence: 99%

Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban

et al. 2020

View full text Add to dashboard Cite

Rivaroxaban (RIV) is commonly prescribed with carbamazepine or phenytoin (CBZ/PHT) in post-stroke seizure or post-stroke epilepsy patients. Although adverse events have been reported in several previous studies when they are coadministered, there are no studies of the interactions between these drugs. Therefore, our study was conducted to solve this lack of information. The potential effects of CBZ/PHT were investigated by comparing the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of RIV between the control group (RIV alone) and the test groups (RIV administered with CBZ/PHT) in rats using the noncompartmental analysis (NCA) and the compartmental model approach. The NCA results indicate that AUCt of RIV decreased by 57.9% or 89.7% and Cmax of RIV decreased by 43.3% or 70.0% after administration of CBZ/PHT, respectively. In addition, both CBZ and PHT generally reduced the effects of RIV on the prothrombin times of the blood samples. PK profiles of RIV were most properly described by a two-compartment disposition model with a mixed first- and zero-order absorption kinetics and a first-order elimination kinetics. The compartmental model approach showed that a 211% or 1030% increase in CL/F of RIV and a 33.9% or 43.4% increase in D2 of RIV were observed in the test groups by the effects of CBZ/PHT, respectively. In conclusion, CBZ and PHT significantly reduced RIV exposure and therefore reduced the therapeutic effects of RIV. Consequently, this might result in adverse events due to insufficient RIV concentration to attain its therapeutic effects. Further studies are needed to validate this finding.

show abstract

Section: Introductionmentioning

confidence: 99%