HEPATOBILIARY EXCRETION OF BERBERINE
- 23 March 2004
- journal article
- research article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Drug Metabolism and Disposition
- Vol. 32 (4), 405-412
- https://doi.org/10.1124/dmd.32.4.405
Abstract
Berberine is a bioactive herbal ingredient isolated from the roots and bark of Berberis aristata or Coptis chinensis. To investigate the detailed pharmacokinetics of berberine and its mechanisms of hepatobiliary excretion, an in vivo microdialysis coupled with high-performance liquid chromatography was performed. In the control group, rats received berberine alone; in the drug-treated group, 10 min before berberine administration, the rats were injected with cyclosporin A (CsA), a P-glycoprotein (P-gp) inhibitor; quinidine, both organic cation transport (OCT) and P-gp inhibitors; SKF-525A (proadifen), a cytochrome P450 inhibitor; and probenecid to inhibit the glucuronidation. The results indicate that berberine displays a linear pharmacokinetic phenomenon in the dosage range from 10 to 20 mg kg-1, since a proportional increase in the area under the concentration-time curve (AUC) of berberine was observed in this dosage range. Moreover, berberine was processed through hepatobiliary excretion against a concentration gradient based on the bile-to-blood distribution ratio (AUCbile/AUCblood); the active berberine efflux might be affected by P-gp and OCT since coadministration of berberine and CsA or quinidine at the same dosage of 10 mg kg-1 significantly decreased the berberine amount in bile. In addition, berberine was metabolized in the liver with phase I demethylation and phase II glucuronidation, as identified by liquid chromatography/tandem mass spectrometry. Also, the phase I metabolism of berberine was partially reduced by SKF-525A treatment, but the phase II glucuronidation of berberine was not obviously affected by probenecid under the present study design.Keywords
This publication has 37 references indexed in Scilit:
- Pharmacokinetics of 5 (and 6)-Carboxy-2′,7′-Dichlorofluorescein and Its Diacetate Promoiety in the LiverThe Journal of pharmacology and experimental therapeutics, 2003
- Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell linesCancer Letters, 2000
- Interactions between P-glycoprotein substrates and other cationic drugs at the hepatic excretory levelBritish Journal of Pharmacology, 1998
- Simultaneous microdialysis sampling from multiple sites in the liver for the study of phenol metabolismLife Sciences, 1996
- Inhibition of In-vitro Lymphocyte Transformation by the Isoquinoline Alkaloid BerberineJournal of Pharmacy and Pharmacology, 1995
- Acute effects of different immunosuppressive drugs on pancreatic, islet, renal, and arterial hepatic blood flow in anesthetized ratsTransplant International, 1994
- Kinetic analysis of hepatobiliary transport of vincristine in perfused rat liver: Possible roles of P-glycoprotein in biliary excretion of vincristineJournal of Hepatology, 1992
- In vitro andin vivo evaluation of the tissue-to-blood partition coefficient for physiological pharmacokinetic modelsJournal of Pharmacokinetics and Biopharmaceutics, 1982
- Heterogeneous distribution of the cytochrome P-450 monooxygenase system in rat liver lobes.The Japanese Journal of Pharmacology, 1982
- Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equationsJournal of Pharmacokinetics and Biopharmaceutics, 1978