Abstract | OBJECTIVE: METHODS: We adopted a high-performance liquid chromatography (HPLC) system to quantify the plasma level of CBZ and its metabolite (carbamazepine-10, 11-epoxide, CBZE). The method was validated as per instructions under United States Food and Drug Administration (USFDA) guidance. For the herb-drug interaction study, rats were randomly divided into four different treatment groups: single-dose CBZ treatment, single-dose CBZ/GR treatment, 2-week course of CBZ treatment and 2-week course of CBZ/GR treatment. RESULTS: Our results demonstrated the auto-induction of CBZ metabolization when comparing single-dose with 2-week course of CBZ treatment. Pharmacokinetic interactions were noted in concomitant use of GR with CBZ by comparing two single-dose treatments (CBZ versus CBZ/GR). Our data showed that GR increased the mean residence time (MRT0-t) and the time taken to reach the maximum concentration (Tmax) of CBZ in single-dose of CBZ/GR treatment. The maximum drug concentration (Cmax) of CBZ was reduced in single-dose CBZ/GR treatment. When comparing the 2-week course of CBZ treatment with the 2-week course of CBZ/GR treatment, the MRT0-t and half-life of CBZ were increased. The AUC0-t, the Cmax and the half-life of CBZE were increased. CONCLUSION: CBZ/GR treatment may reduce the auto-induction of CBZ over 2 weeks. While the reduction of auto-induction could enhance the therapeutic effects of CBZ, it could also lead to an increase in neurological side effects and non-neurological adverse effects. Our results provided preclinical evidence of herb-drug interaction, which may have implications for epilepsy patients treated with GR.
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Authors | Ka Lai Yip, Xuelin Zhou, Ping Chook, Ping Chung Leung, Steven Schachter, Vincent C T Mok, Thomas W H Leung, Chi Man Koon, Howan Leung |
Journal | Epilepsy research
(Epilepsy Res)
Vol. 165
Pg. 106376
(09 2020)
ISSN: 1872-6844 [Electronic] Netherlands |
PMID | 32526641
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier B.V. All rights reserved. |
Chemical References |
- Anticonvulsants
- Benzodiazepines
- Carbamazepine
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Topics |
- Animals
- Anticonvulsants
(pharmacology)
- Benzodiazepines
(pharmacology)
- Carbamazepine
(analogs & derivatives, pharmacology)
- Chromatography, High Pressure Liquid
(methods)
- Drug Interactions
(physiology)
- Epilepsy
(drug therapy)
- Herb-Drug Interactions
(physiology)
- Rats, Sprague-Dawley
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