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Lei H.-P.,Guangdong Academy of Medical science | Yu X.-Y.,Guangdong Academy of Medical science | Xie H.-T.,Central South University | Xie H.-T.,Anhui Provincial Center for Drug Clinical Evaluation | And 5 more authors.
Xenobiotica | Year: 2010

The objective of this study was to investigate the effects of continuous St. John's wort administration on single-dose pharmacokinetics of bupropion, a substrate of cytochrome P450 (CYP) 2B6, in healthy Chinese volunteers. Eighteen unrelated healthy male subjects participated in this study. The single-dose pharmacokinetics of bupropion and hydroxybupropion were determined before (control) and after a long-term period of St. John's wort intake (325mg, three times a day for 14 days). Plasma concentrations of bupropion and hydroxybupropion were determined before and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60 and 72h after dosing. St. John's wort treatment decreased the area under the concentration versus time curve extrapolated to infinity of bupropion in healthy volunteers from 1.4 μg·h ml-1 (95% confidence interval [CI]1.21.6 μg·h ml-1) after bupropion alone to 1.2 μg·h ml-1 (95% CI1.11.3 μg·h ml -1) during St. John's wort treatment. St. John's wort treatment increased the oral clearance of bupropion from 108.3 l h-1 (95% CI95.4123.0 l h-1) to 130.0 l h-1 (95% CI118.4142.7 l h-1). No change in the time to peak concentration (tmax) and the blood elimination half-life (t1/2) of bupropion was observed between the control and St. John's wort-treated phases. However, the half-life of hydroxybupropion between two phases had a significant difference by a Student's t test after logarithmic transformation. St. John's wort treatment decreased the half-life of hydroxybupropion from 26.7h (95% CI23.829.9h) to 24.4h (95% CI21.927.3h). St. John's wort decreased, to a statistically significant extent, the plasma concentrations of bupropion, probably mainly by increasing the clearance of bupropion. © 2010 Informa UK Ltd.

Chen Q.,Anhui Provincial Center for Drug Clinical Evaluation | Xie H.-T.,Anhui Provincial Center for Drug Clinical Evaluation | Li Y.,Wannan Medical College | Wang G.,Central South University | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2015

This study aims at establishing and validating an in vitro system to screen drug inducers of CYPs mediated via hPXR, as well as studying transcriptional regulation of CYPs mediated via hPXR by helicid and its two metabolites. Methods. Cloning the nuclear receptor hPXR and the promoters of CYP3A4, CYP2B6, CYP2C9, and inserting the trans-element to the upstream of firefly luciferase reporter gene of the pGL4.17 vectors, then cotransfecting the report vectors and hPXR expression plasmid to HepG2 cell line. After 24 hours, the transfected cells were treated with helicid (0.004, 0.04, and 0.4 μmol/L) and its metabolite I and metabolite II (0.0004, 0.004, and 0.04 μmol/L) for 48 h, while rifampin (10 μmol/L) was included as the positive control and 0.1% DMSO as the negative control group. Cells were lysized and luciferase activity was determined using a dual luciferase reporter assay kit. Results. Helicid and its metabolites did not significantly increase promoter activities of CYP3A4, CYP2B6, and CYP2C9 in HepG2 cells transfected with PXR expression plasmid (P > 0.05). Conclusion. PXR-expressed CYP3A4, CYP2B6, and CYP2C9 dual luciferase reporter gene platforms were successfully established, and helicid and its metabolites I, II do not significantly induce the transcription of CYP3A4, CYP2B6, and CYP2C9. © 2015 Qun Chen et al.

Jia Y.,China Pharmaceutical University | Jia Y.,Anhui Provincial Center for Drug Clinical Evaluation | Xie H.,Anhui Provincial Center for Drug Clinical Evaluation | Xie H.,Central South University | And 10 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2010

A simple liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) method with highly improved sensitivities for the determination of helicid in rat bile, urine, feces and most tissues was developed. The tissues and feces were firstly homogenized mechanically using deionized water as the media. Bile, urine, tissues and feces homogenates were extracted by liquid-liquid extraction with n-butyl alcohol for sample preparation. The subsequent analysis procedures were performed on a Shimadzu LCMS2010A system (electrospray ionization single quadrupole mass analyzer). A Luna C18 column (150 mm × 2.00 mm, 5 μm) was used as the analytical column, while a mixture of acetonitrile and ammonium chloride water solution was used as the mobile phase. The proportions of mobile phase were changed timely according to gradient programs. Chlorinated adducts of molecular ions [M+Cl]- at m/z 319.00 and 363.05 were used to quantify helicid and bergeninum (internal standard), respectively. The method was validated to be accurate, precise and rugged with good linearity. The proposed method was successfully applied to the preclinical tissue distribution and excretion studies of helicid in rats. © 2010 Elsevier B.V. All rights reserved.

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