Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence

The AAPS Journal
Chunming LyuZhong Zuo

Abstract

Veratramine, a major alkaloid from Veratrum nigrum L., has distinct anti-tumor and anti-hypertension effects. Our previous study indicated that veratramine had severe toxicity toward male rats. In order to elucidate the underling mechanism, in vivo pharmacokinetic experiments and in vitro mechanistic studies have been conducted. Veratramine was administrated to male and female rats intravenously via the jugular vein at a dose of 50 μg/kg or orally via gavage at 20 mg/kg. As a result, significant pharmacokinetic differences were observed between male and female rats after oral administration with much lower concentrations of veratramine and 7-hydroxyl-veratramine and higher concentrations of veratramine-3-O-sulfate found in the plasma and urine of female rats. The absolute bioavailability of veratramine was 0.9% in female rats and 22.5% in male rats. Further experiments of veratramine on Caco-2 cell monolayer model and in vitro incubation with GI content or rat intestinal subcellular fractions demonstrated that its efficient passive diffusion mediated absorption with minimal intestinal metabolism, suggesting no gender-related difference during its absorption process. When veratramine was incubated with male or female rat liver m...Continue Reading

References

Jan 1, 1992·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P Soucek, I Gut
Mar 29, 1991·Biochemical and Biophysical Research Communications·M Runge-Morris, J Wilusz
Jan 1, 1991·Japanese Journal of Pharmacology·R NagataT Fukuda
Jan 1, 1982·Reviews of Physiology, Biochemistry and Pharmacology·P Honerjäger
Jan 1, 1993·The Biochemical Journal·K A ComerC N Falany
Aug 1, 1996·Archives of Biochemistry and Biophysics·A GhosalP E Thomas
Feb 14, 1998·Journal of Natural Products·K A el Sayed
May 5, 1998·Chemico-biological Interactions·C D KlaassenR T Dunn
Apr 4, 2000·Toxicological Sciences : an Official Journal of the Society of Toxicology·L H PottengerJ M Waechter
Mar 20, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Matthew Hutzler, Timothy S Tracy
Jun 17, 2003·Chemical Research in Toxicology·Ge LinXiao-Quan Liu
May 29, 2004·Pharmacogenetics·Rebecca L BlanchardMichael W H Coughtrie
May 6, 1950·Journal of the American Medical Association·W S COEJ M KINSMAN
Dec 3, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Niranjali GamageMichael E McManus
Nov 28, 2006·Expert Opinion on Drug Metabolism & Toxicology·Marcella MartignoniRuben de Kanter
Jan 24, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ge LinJiang Zheng
May 18, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Li ZhangZhong Zuo
Oct 31, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Walter MeinlAlfonso Lampen
Jan 4, 2008·The AAPS Journal·Mario L RocciPaula Jardieu
Feb 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Anuradha RaoPaul A Dawson
Mar 12, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Doreen MitschkeUrsula Moenning
Jun 24, 2008·Phytotherapy Research : PTR·Jian TangWei-Dong Zhang
Sep 24, 2008·International Journal of Pharmaceutics·Yin Cheong WongZhong Zuo
Oct 10, 2008·Journal of Medicinal Chemistry·Martin R TremblayJulian Adams
Nov 1, 1948·American Heart Journal·E D FREIS, J R STANTON
Jan 24, 2009·Se pu = Chinese journal of chromatography·Hongyan ZhangShengqi Wang
Mar 14, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Walter MeinlHansruedi Glatt
Mar 25, 2009·Journal of Medicinal Chemistry·Neeraj MahindrooNaoaki Fujii
Jun 26, 2009·Organic Letters·Jeffrey D WinklerNadia Dahmane
Dec 17, 2009·Phytotherapy Research : PTR·Jian TangWei-Dong Zhang
Apr 30, 2010·Angewandte Chemie·Philipp HeretschAthanassios Giannis
May 8, 2010·Current Drug Metabolism·Wei-Zhu ZhongShinji Yamazaki

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