Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban
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 drug...
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doaj-8f8ec24bb6c745ddb428f2fc518730732020-11-25T04:08:39ZengMDPI AGPharmaceutics1999-49232020-10-01121040104010.3390/pharmaceutics12111040Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of RivaroxabanLien Thi Ngo0Sung-yoon Yang1Quyen Thi Tran2Sang Kyum Kim3Hwi-yeol Yun4Jung-woo Chae5College of Pharmacy, Chungnam National University, Daejeon 305764, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 305764, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 305764, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 305764, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 305764, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 305764, KoreaRivaroxaban (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 <i>AUC<sub>t</sub></i> of RIV decreased by 57.9% or 89.7% and <i>C<sub>max</sub></i> 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 <i>CL/F</i> of RIV and a 33.9% or 43.4% increase in <i>D</i>2 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.https://www.mdpi.com/1999-4923/12/11/1040rivaroxabancarbamazepinephenytoindrug interactionpharmacokineticspharmacodynamics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lien Thi Ngo Sung-yoon Yang Quyen Thi Tran Sang Kyum Kim Hwi-yeol Yun Jung-woo Chae |
spellingShingle |
Lien Thi Ngo Sung-yoon Yang Quyen Thi Tran Sang Kyum Kim Hwi-yeol Yun Jung-woo Chae Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban Pharmaceutics rivaroxaban carbamazepine phenytoin drug interaction pharmacokinetics pharmacodynamics |
author_facet |
Lien Thi Ngo Sung-yoon Yang Quyen Thi Tran Sang Kyum Kim Hwi-yeol Yun Jung-woo Chae |
author_sort |
Lien Thi Ngo |
title |
Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban |
title_short |
Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban |
title_full |
Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban |
title_fullStr |
Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban |
title_full_unstemmed |
Effects of Carbamazepine and Phenytoin on Pharmacokinetics and Pharmacodynamics of Rivaroxaban |
title_sort |
effects of carbamazepine and phenytoin on pharmacokinetics and pharmacodynamics of rivaroxaban |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2020-10-01 |
description |
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 <i>AUC<sub>t</sub></i> of RIV decreased by 57.9% or 89.7% and <i>C<sub>max</sub></i> 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 <i>CL/F</i> of RIV and a 33.9% or 43.4% increase in <i>D</i>2 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. |
topic |
rivaroxaban carbamazepine phenytoin drug interaction pharmacokinetics pharmacodynamics |
url |
https://www.mdpi.com/1999-4923/12/11/1040 |
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