Disposition of orally administered a promising chemotherapeutic agent flavopiridol in the intestine

Drug Development and Industrial Pharmacy
Bijun XiaZhongqiu Liu

Abstract

Flavopiridol (FLAP) is a promising chemotherapeutic agent undergoing clinical phase I and phase II trials, and a number of studies have elucidated its hepatic metabolism and biliary disposition. In present study, the intestinal disposition of orally administered FLAP was characterized through pharmacokinetic studies in rats as well as absorption and metabolism studies using a Caco-2 cell culture and four-site perfused rat intestinal models. Pharmacokinetic results show that FLAP has high bioavailability (> 75%), long T1/2 (> 260 min), and short peak time (<20 min). In the Caco-2 cell culture model, the bidirectional permeability of FLAP was 0.47 × 10(-5) cm/s to 1.53 × 10(-5) cm/s and the efflux ratios were 3.27 and 2.17 at 10 and 30 μM, respectively. Apical loading of two P-glycoprotein (P-gp) inhibitors, cyclosporine A and verapamil, significantly increased the intracellular amount of FLAP and lowered its efflux ratio. In the four-site model, 10 and 40 μM FLAP perfusions were well absorbed at various regions of the intestine, and the biliary excretions of FLAP glucuronides were 1.60-2.84 nmol and 12.47-17.33 nmol, respectively. FLAP possesses high oral bioavailability and good absorption in the intestine, in which FLAP may be...Continue Reading

References

Apr 20, 2001·Critical Reviews in Oncology/hematology·H H Sedlacek
May 18, 2001·British Journal of Cancer·S A BoernerK C Bible
Apr 30, 2002·The Annals of Pharmacotherapy·Suoping ZhaiWilliam D Figg
Feb 27, 2003·The Journal of Pharmacology and Experimental Therapeutics·Jun ChenMing Hu
Nov 25, 2003·The Journal of Alternative and Complementary Medicine : Research on Paradigm, Practice, and Policy·Yong LiuMing Hu
Mar 17, 2004·The Journal of Pharmacology and Experimental Therapeutics·Eun Ju JeongMing Hu
Jun 3, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John C ByrdUNKNOWN Cancer and Leukemia Group B
May 10, 2006·Investigational New Drugs·Basil F El-RayesPhilip A Philip
Aug 3, 2006·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stephen W J WangMing Hu
Oct 13, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Huadong Sun, K Sandy Pang
Jul 2, 2009·Pharmaceutical Research·Sarah Shugarts, Leslie Z Benet
Oct 15, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thomas S LinJohn C Byrd
Dec 17, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Thomas S LinJohn C Byrd

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