title: Absorptive interactions of concurrent oral administration of (+)-catechin and puerarin in rats and the underlying mechanisms.
abstract: OBJECTIVE
  (+)-Catechin and puerarin are polyphenol and flavonoid, respectively, in green tea and foodstuffs. They exhibit potent antioxidant activity and are widely used for treating cardiocerebrovascular diseases. The aim of this work was to investigate the potential interactions between (+)-catechin and puerarin following concurrent oral administration in rats, and their absorption mechanisms in Caco-2 cell monolayers.
  
  
  METHODS
  Pharmacokinetic studies were conducted in male rats received (+)-catechin (140 mg/kg, po) and/or puerarin (200 mg/kg, po). The cell uptake and transport behavior in Caco-2 cell monolayers and the interactions of the two compounds were analyzed.
  
  
  RESULTS
  When (+)-catechin and puerarin were administered concurrently, the AUC0-12 h and Cmax values of puerarin were 2.48-fold and 3.91-fold, respectively, as large as those of puerarin alone; the AUC0-12 h and Cmax values of (+)-catechin were decreased to 57.62% and 77.55%, respectively, compared with those of (+)-catechin alone. In Caco-2 cell monolayers, (+)-catechin (300 and 600 μmol/L) significantly increased the cell uptake and transport of puerarin, whereas puerarin (300 and 600 μmol/L) significantly decreased the cellular uptake and transport of (+)-catechin. Furthermore, both cyclosporine A (P-glycoprotein inhibitor) and MK-571 (MRP-2 inhibitor) significantly increased the cellular uptake and transport of (+)-catechin and puerarin.
  
  
  CONCLUSIONS
  Concurrent oral administration of (+)-catechin and puerarin significantly increased the absolute oral bioavailability of puerarin, but decreasing that of (+)-catechin. The competitive efflux of (+)-catechin and puerarin by P-glycoprotein and MRP-2 might lead to this interaction during their absorption process in the small intestine.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Hui-fang
authors.initials: HF
authors.lastname: Su
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xin-yi
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Zhi-rong
authors.initials: ZR
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D065567:Absorption, Physiological; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002392:Catechin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016572:Cyclosporine / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002392:Catechin; D016572:Cyclosporine; D007529:Isoflavones; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011422:Propionates; D011804:Quinolines; C000715087:ABCC2 protein, human; C059141:verlukast; C033607:puerarin