ArticleThe AAPS journal2019
Reduced Systemic and Brain Exposure with Inhibited Liver Metabolism of Carbamazepine After Its Long-Term Combination Treatment with Piperine for Epilepsy Control in Rats.
Article in The AAPS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- A Systematic Review of the Anti-seizure and Antiepileptic Effects and Mechanisms of Piperine.Central nervous system agents in medicinal chemistry · 2025Pooled it
- Article
- Safety Aspects of the Use of Isolated Piperine Ingested as a Bolus.Foods (Basel, Switzerland) · 2021Review
- Comparing the Effect of Piperine and Ilepcimide on the Pharmacokinetics of Curcumin in SD Rats.Frontiers in pharmacology · 2021Article
- Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Carbamazepine (CBZ) with piperine, the active ingredient in black pepper, which is omnipresent in food and may be potentially used for epilepsy control owing to its anticonvulsant effects, can be coadministered to epileptic patients. Since piperine has previously demonstrated its inhibition of the CYP3A-mediated metabolism of CBZ to carbamazepine-10,11-epoxide (CBZE), the present study aimed to investigate the impact of piperine on CBZ pharmacokinetics (PKs) in rats and pharmacodynamics in zebrafish and mouse acute seizure models. Plasma and brain PKs were studied in rats after a single-dose or 2-week combined oral administration of piperine (3.5/35 mg/kg, q.d.) and CBZ (40 mg/kg, t.i.d.) by blood sampling and brain microdialysis. Although no PK change was noticed after a single coadministration, significantly decreased plasma and brain concentrations of CBZ and CBZE with inhibited rat liver Cyp3a2 were demonstrated after long-term combined administration. Our developed compartmental model for the PK characterization of CBZ and CBZE in the blood and brain further estimated that coadministration with high-dose piperine could lead to decreases of 26%, 35%, and 38% in bioavailability, metabolism, and brain uptake of CBZ, respectively. Regardless of the PK changes, a limited impact on the antiepileptic effect of CBZ was found after the coadministration of CBZ and piperine in the tested seizure models. In conclusion, single-dose cotreatment of CBZ and piperine did not result in any significant PK or pharmacodynamic interactions, whereas their long-term cotreatment could lead to inhibited liver metabolism and the markedly reduced systemic and brain exposure of CBZ and CBZE.
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