European Journal of Clinical Pharmacology

, Volume 68, Issue 2, pp 213–217

Repeated administration of berberine inhibits cytochromes P450 in humans

Short Communication

DOI: 10.1007/s00228-011-1108-2

Cite this article as:
Guo, Y., Chen, Y., Tan, Z. et al. Eur J Clin Pharmacol (2012) 68: 213. doi:10.1007/s00228-011-1108-2

Abstract

Purpose

Berberine is a plant alkaloid that is widely used to treat gastrointestinal infections, diabetes, hypertension, and hypercholesterolemia. Many studies have reported interactions between berberine-containing products and cytochromes P450 (CYPs), but little is known about whether berberine alters CYP activities in humans, especially after repeated doses.

Methods

A two-phase randomized-crossover clinical study in healthy male subjects was performed. After 2 weeks of berberine (300 mg, t.i.d., p.o.) administration, midazolam, omeprazole, dextromethorphan, losartan, and caffeine were used to evaluate enzyme activities of CYP3A4, 2C19, 2D6, 2C9, and CYP1A2, respectively.

Results

A decrease in CYP2D6 activity was observed as the 0–8 h urinary dextromethorphan/dextrorphan increased ninefold (P < 0.01). In addition, losartan/E-3174 ratio doubled (P < 0.01) after BBR administration, indicating a decrease in CYP2C9 activity. CYP3A4 activity was also inhibited, as the Cmax, AUC0–∞, and AUC0–12 of midazolam were increased 38% (P < 0.05), 40% (P < 0.01), and 37% (P < 0.05) after BBR treatment, respectively. Compared with the placebo period, the Tmax and T1/2 of midazolam during BBR administration were prolonged from 3.03 ± 0.27 to 3.66 ± 0.37 h and 0.66 ± 0.08 to 0.99 ± 0.09 h, respectively; the oral clearance of midazolam was decreased 27% (P < 0.05); and the phenotypic indices of 1 h midazolam/1′-hydroxymidazolam increased 59% (P < 0.01). There were no statistically significant differences in the pharmacokinetic parameters of the other probe drugs between placebo and the BBR-treated group.

Conclusions

Repeated administration of berberine (300 mg, t.i.d., p.o.) decreased CYP2D6, 2C9, and CYP3A4 activities. Drug-drug interactions should be considered when berberine is administered.

Keywords

BerberineCYP2D6CYP2C9CYP3A4Humans

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Pharmacogenetics Research Institute, Institute of Clinical PharmacologyCentral South University, XiangYa School of MedicineChangshaPeople’s Republic of China
  2. 2.Department of Pharmacology, Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityUSA