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Predict more pgp - ligand interactions now!

1. PLoS One. 2012;7(2):e31312. Epub 2012 Feb 16.

Impact of the Herbal Medicine Sophora flavescens on the Oral Pharmacokinetics of
Indinavir in Rats: The Involvement of CYP3A and P-Glycoprotein.

Yang JM, Ip SP, Xian Y, Zhao M, Lin ZX, Yeung JH, Chan RC, Lee SS, Che CT.

School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong

Sophora flavescens is a Chinese medicinal herb used for the treatment of
gastrointestinal hemorrhage, skin diseases, pyretic stranguria and viral
hepatitis. In this study the herb-drug interactions between S. flavescens and
indinavir, a protease inhibitor for HIV treatment, were evaluated in rats.
Concomitant oral administration of Sophora extract (0.158 g/kg or 0.63 g/kg,
p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a
dose-dependent decrease of plasma indinavir concentrations, with 55%-83% decrease
in AUC(0-∞) and 38%-78% reduction in C(max). The CL (Clearance)/F (fraction of
dose available in the systemic circulation) increased up to 7.4-fold in
Sophora-treated rats. Oxymatrine treatment (45 mg/kg, p.o.) also decreased
indinavir concentrations, while the ethyl acetate fraction of Sophora extract had
no effect. Urinary indinavir (24-h) was reduced, while the fraction of indinavir
in faeces was increased after Sophora treatment. Compared to the controls,
multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp
in the small intestine and liver. In addition, Sophora treatment increased
intestinal and hepatic mRNA expression of CYP3A1, but had less effect on CYP3A2
expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by
Sophora treatment, hepatic CYP3A activity increased in the Sophora-treated rats.
All available data demonstrated that Sophora flavescens reduced plasma indinavir
concentration after multiple concomitant doses, possibly through hepatic CYP3A
activity and induction of intestinal and hepatic P-gp. The animal study would be
useful for predicting potential interactions between natural products and oral
pharmaceutics and understanding the mechanisms prior to human studies. Results in
the current study suggest that patients using indinavir might be cautioned in the
use of S. flavescens extract or Sophora-derived products.

PMCID: PMC3281083
PMID: 22359586 [PubMed - in process]