The Effects of Different Administration Regimens of Berberine Hydrochloride on the Pharmacokinetics of Sirolimus in Rats
Open accessAbstract
ABSTRACT Sirolimus is a third‐generation immunosuppressant with multiple efficacies, including antifungal, antitumor, and immunosuppressive properties. We conducted a pharmacokinetic study to determine the effect of berberine hydrochloride (BBR) on the pharmacokinetics of sirolimus in rats. Thirty‐six rats were randomly divided into six groups, and blood samples were collected from the posterior orbital venous plexus at different time points after the last administration to determine the plasma concentration of sirolimus. Liquid chromatography tandem mass spectrometry (LC–MS/MS) was used for detection, and DAS 2.0 software was employed for pharmacokinetic analysis. A single administration of BBR significantly reduced the pharmacokinetic parameter AUC0‐12h of sirolimus. Repeated administration of BBR resulted in an upward trend in Cmax AUC0‐12h, AUC0‐∞, and CLz all show an upward trend. This study indicates that BBR has a certain impact on the pharmacokinetics of sirolimus in rats. However, further validation of the role of gene polymorphism in pharmacokinetics and clinical efficacy is needed for further research in a wider population.
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A 2025 pharmacokinetic study in rats showed that different administration regimens of berberine hydrochloride alter exposure to sirolimus, supporting extension of the interaction signal from cyclosporine to the whole class of calcineurin and mTOR inhibitors.
“A 2025 pharmacokinetic study in rats showed that different administration regimens of berberine hydrochloride alter exposure to sirolimus, a CYP3A/P-gp substrate, supporting extension of the interaction signal from cyclosporine to the whole class of calcineurin and mTOR inhibitors [81].”
From Berberine-Drug Interactions: Mechanisms, Clinical Relevance and Risk Stratification-A Narrative Review (2026) · cites this paper as [81]
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Cites
mTOR-targeted therapy of cancer with rapamycin derivatives
Vignot, S., Faivre, S. J., de Aguirre, & Raymond, É. (2005) · Annals of Oncology · doi:10.1093/annonc/mdi113 · Cited by 613 · see citing works
Use of Sirolimus in Solid Organ Transplantation
Augustine, J. J., Bodziak, K. A., & Hricik, D. E. (2007) · Drugs · doi:10.2165/00003495-200767030-00004 · Cited by 248 · see citing works
McCrea, J. B., Macha, S., Adedoyin, A. B., Marshall, W., Menzel, K., Cho, C. R., Liu, F., Zhao, T. X., Levine, V., Kraft, W. K., et al. (2019) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1423 · Cited by 86 · see citing works
Djebli, N., Rousseau, A., Hoizey, G., Rérolle, J.-P., Toupance, O., Meur, Y. L., & Marquet, P. (2006) · Clinical Pharmacokinetics · doi:10.2165/00003088-200645110-00007 · Cited by 77 · see citing works
Kwon, M., Lim, D. Y., Lee, C. H., Jeon, J.-H., Choi, M.-K., & Song, I.-S. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12090882 · Cited by 76 · see citing works
Alolga, R. N., Fan, Y., Chen, Z., Liu, L., Zhao, Y., Li, J., Chen, Y., Lai, M., Li, P., & Qi, L. (2016) · Scientific Reports · doi:10.1038/srep27671 · Cited by 57 · see citing works
Poor Tolerance of Sirolimus in a Steroid Avoidance Regimen for Renal Transplantation
Smith, M. W., Newstead, C. G., Ahmad, N., Lewington, A. J. P., Tibble, S., Lodge, J. P. A., Pollard, S. G., & Baker, R. J. (2008) · Transplantation · doi:10.1097/tp.0b013e3181613e65 · Cited by 28 · see citing works
Feltrin, C., Farias, I. V., Sandjo, L. P., Reginatto, F. H., & Simões, C. M. O. (2020) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.0c00182 · Cited by 26 · see citing works
Cui, H., Wang, J., Zhang, Q., Dang, M.-M., Liu, H., Dong, Y. J., Zhang, L., Yang, F., Wu, J., & Tong, X. (2016) · Molecules · doi:10.3390/molecules21040464 · Cited by 21 · see citing works
Infigratinib Is a Reversible Inhibitor and Mechanism-Based Inactivator of Cytochrome P450 3A4
Tang, L. W. T., Teng, J. W., Verma, R. K., Koh, S. K., Zhou, L., Go, M., Fan, H., & Chan, E. C. Y. (2021) · Drug Metabolism and Disposition · doi:10.1124/dmd.121.000508 · Cited by 21 · see citing works
Li, Q., Yang, Y., Zhou, T., Wang, R., Li, N., Zheng, M., Li, Y., Zhang, J., Wu, F., Yang, B., et al. (2018) · Molecules · doi:10.3390/molecules23082042 · Cited by 18 · see citing works
Self-citationThe Intracellular Mechanism of Berberine-Induced Inhibition of CYP3A4 Activity
Feng, P.-F., Zhu, L.-X., Jie, J., Yang, P., & Chen, X. (2021) · Current Pharmaceutical Design · doi:10.2174/1381612827666210715155809 · Cited by 15 · see citing works
Effects of berberine on pharmacokinetics of midazolam and rhodamine 123 in rats in vivo
Xin, H., Tang, X., Ouyang, M., Zhong, J.-X., & Li, W.-L. (2016) · SpringerPlus · doi:10.1186/s40064-016-2013-z · Cited by 14 · see citing works
Nilles, J., Weiß, J., Sauter, M., Haefeli, W. E., Ruez, S., & Theile, D. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03531-2 · Cited by 13 · see citing works
Zhang, Z., Hu, Q., Yang, C., Chen, M., & Han, B. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2282180 · Cited by 13 · see citing works
Polic, V., Sevrioukova, I. F., & Auclair, K. (2018) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2018.06.014 · Cited by 10 · see citing works
Effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in hyperlipidemia rats
Wu, F., Cui, M., Wang, S., Yu, C., Yin, W., Li, J., & Yan, X. (2023) · Xenobiotica · doi:10.1080/00498254.2023.2290648 · Cited by 10 · see citing works
A patent review of CYP3A4 inhibitors (2018 – present)
Tu, D., Hu, X., Lei, J.-X., Liu, S., Xiao, Z.-P., Yang, L., & Ge, G. (2025) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2025.2470294 · Cited by 10 · see citing works
CYPSI: a structure-based interface for cytochrome P450s and ligands in Arabidopsis thaliana
Zhang, G., Zhang, Y., & Su, Z. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-332 · Cited by 6 · see citing works
Self-citationMatsuda, A., Karch, R., Bauer, M., Traxl, A., Zeitlinger, M. A., & Langer, O. (2017) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2017.03.024 · Cited by 5 · see citing works
In vivo pharmacokinetics of ginsenoside compound K mediated by gut microbiota
Deng, M., Huang, S.-T.-Z., Xu, Y., Shao, L., Wang, Z.-G., Liang-jian, C. H. E. N., & Huang, W. (2024) · PLoS ONE · doi:10.1371/journal.pone.0307286 · Cited by 5 · see citing works
Wang, M., Duan, B.-L., Yuan, Y.-J., Su, X., Zheng, H., Wang, F., & Sun, H. (2016) · International Journal of Clinical Pharmacology and Therapeutics · doi:10.5414/cp202499 · Cited by 4 · see citing works
Flagged first, then by citations
1 of the 23 references couldn’t be matched to a known paper.
Research works printed but not linked: 7
- [3]W. Wang, C. Zhang, and X. Tang, “ Research Progress on Clinical Application and Drug Interactions of Sirolimus,” Journal of Clinical Rational Drug Use 11, no. 31 (2018): 173– 177.
- [16]Y. Wang, S. Wang, X. Yang, et al., “ Study on the Pharmacokinetics of Xianlingpi Granules In Vivo Based on UPLC‐QQQ‐MS Technology,” Journal of Central South Pharmacy 22, no. 4 (2024): 930– 936.
- [18]Y. Zhao, Z. Xu, Y. Liu, et al., “ Research Progress on Cytochrome P450 Gene Polymorphism and Drug Metabolism,” Journal of Clinical Drug Therapy 15, no. 4 (2017): 1– 6.
- [19]P. Xie and H. Song, “ Research Progress in Monitoring Sirolimus Blood Concentration,” Chinese Pharmacy 26, no. 32 (2015): 4604– 4606.
- [20]X. Ren, L. Chen, Y. Zhang, et al., “ Systematic Evaluation of the Effect of Drug Gene Polymorphism on Sirolimus Blood Concentration in Renal Transplant Recipients,” Journal of Medicine and Pharmacy 41, no. 4 (2022): 449– 457.
- [22]W. Huo, “ Literature Analysis of Adverse Reactions Caused by Sirolimus After Renal Transplantation,” Chinese Journal of Tissue Engineering Research and Clinical Rehabilitation 14, no. 31 (2010): 5825– 5828.
- [23]Q. Ding and D. Feng, “ Meta‐Analysis of CYP3A5 Gene Polymorphism and Sirolimus Pharmacokinetics in Renal Transplant Recipients,” Journal of PLA Pharmaceutical Sciences 32, no. 1 (2016): 66– 68.
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Sorted by citations
Dumitru, C. N., Marcu, T., Dumitru, A. O., Tudor, S. S., Ferțu, I. D., Elisei, A.-M., & Goroftei, L. (2026) · Pharmaceuticals · doi:10.3390/ph19081313 · Cited by 2 · see citing works
“A 2025 pharmacokinetic study in rats showed that different administration regimens of berberine hydrochloride alter exposure to sirolimus, a CYP3A/P-gp substrate, supporting extension of the interaction signal from cyclosporine to the whole class of calcineurin and mTOR inhibitors [81].”
Alotaibi, A. A., Habib, S. S., Gad, H. I., Doheyan, T. A., Aldosary, M., Aljasham, A., Alotaibi, A., Alshawakir, Y., & Al-Masri, A. (2026) · Saudi Pharmaceutical Journal · doi:10.1007/s44446-026-00074-2 · Cited by 1 · see citing works
Chen, H., Adu‐Frimpong, M., Yuan, L., Yang, Y., Berdiyar, J., Yu, J., Cao, X., Wang, Q., & Xu, X. (2025) · Journal of drug targeting · doi:10.1080/1061186x.2025.2576120
Self-citationAnyanwu, G. E., Ekwueme, P. E., Nsan, A., Ezeugwu, L., Ogbe, P. C., Anyanwu, C. N., Ojiakor, V. O., & Ugwu, C. P. O. (2026) · Nutritional Neuroscience · doi:10.1080/1028415x.2026.2684552
- Authors
- Yang, Y., Zhang, Y., Qu, Y., & Cui, L.
- Affiliations
- ShenZhen People’s Hospital (CN)
- Corresponding author
- Cui, Liwan
- ORCID
- Venue
- Pharmacology Research & Perspectives
- Publisher
- Wiley
- Published
- 2025-05-21
- Volume
- 13
- Issue
- 3
- Pages
- e70126-e70126
- ISSN
- 2052-1707 (ISSN-L)
- PMC
- PMC12093149
- OpenAlex
- W4410565832
- Cited by
- 4
- References
- 23
- Citations by year
- 2026: 3 · 2025: 1
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmacology Research & Perspectives (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Guangdong Provincial Hospital of Traditional Chinese Medicine
- Topics
- Health Sciences › Medicine › Pharmacology › Berberine and alkaloids research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- berberine hydrochloride, rapamycin, pharmacokinetics, drug-drug interactions, immunosuppressants, repeated administration, plasma concentration, rats
- MeSH terms
- Animals, Berberine, Chromatography, Liquid, Drug Interactions, Immunosuppressive Agents, Male, Rats, Sprague-Dawley, Area Under Curve, Sirolimus, Rats, Tandem Mass Spectrometry
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