Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp
Abstract
The in vivo effects of berberine (BBR), the widely used bioactive herbal ingredient from many traditional Chinese medicinal herbs, on the pharmacokinetics of carbamazepine (CBZ, a substrate of CYP3A) and its metabolite carbamazepine 10,11-epoxide (ECBZ), digoxin (DIG, a substrate of P-gp) and cyclosporine A (CsA, a dual substrate of CYP3A and P-gp) were evaluated in rats. After a 2-week pretreatment with BBR, the pharmacokinetic parameters of i.g. administered CBZ and ECBZ were not significantly altered. The pharmacokinetics of i.v. administered DIG was not modified by single and 2-week pretreatments with BBR, but a dose-dependent increase in AUC and C(max) was observed in the i.g. administered DIG parameters in rats. The AUCs of DIG with BBR (30 mg/kg, 100 mg/kg) were 133%, 170% (single) and 123%, 169% (2-week) of control, respectively. The AUC and C(max) of i.g. administered CsA with a 2-week pretreatment with BBR increased by 62% and 43% (BBR 30 mg/kg, p < 0.05), 96% and 60% (BBR 100 mg/kg, p < 0.01), compared with the control. In conclusion, berberine produced a dose-dependent increased bioavailability of digoxin and cyclosporine A by inhibition of intestinal P-gp. No significant changes in CYP3A activity by berberine were observed.
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In preclinical models, berberine increases the bioavailability of digoxin and cyclosporine through inhibition of intestinal P-glycoprotein; for digoxin the increase was dose-dependent and occurred only after intragastric, not intravenous, administration.
“In preclinical models, berberine increases the bioavailability of digoxin and cyclosporine, two classic P-gp substrates, through inhibition of intestinal P-gp; for digoxin the increase in exposure was dose-dependent and occurred only after intragastric, not intravenous, administration, consistent with an intestinal site of interaction [79,80].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [80]
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- Authors
- Qiu, W., Jiang, X. H., Liu, C. X., Ju, Y., & Jin, J. X.
- Affiliations
- Sichuan University (CN)
- Tianjin Institute of Pharmaceutical Research (China) (CN)
- Lanzhou University Second Hospital (CN)
- Corresponding author
- Jiang, X. H.
- ORCID
- Jiang, X. H.
- Venue
- Phytotherapy Research
- Publisher
- Wiley
- Published
- 2009-10-23
- Volume
- 23
- Issue
- 11
- Pages
- 1553-1558
- ISSN
- 0951-418X (ISSN-L)
- 1099-1573
- OpenAlex
- W2059880023
- Cited by
- 64
- References
- 21
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 7
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Phytotherapy Research (publishedVersion)
- PubMed (publishedVersion)
- Lanzhou University Institutional Repository (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Keywords
- berberine, pharmacokinetics, CYP3A, P-glycoprotein, carbamazepine, carbamazepine-10,11-epoxide, digoxin, cyclosporine, drug-drug interactions, bioavailability, herbal medicine, rats
- MeSH terms
- Animals, Berberine, Biological Availability, Carbamazepine, Digoxin, Drug Interactions, Male, Cyclosporine, Rats, Wistar, Area Under Curve, ATP Binding Cassette Transporter, Subfamily B, Member 1, Rats, Cytochrome P-450 CYP3A
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