title: Pharmacokinetic interaction between scutellarin and valsartan in rats.
abstract: Scutellarin is the main effective constituent of breviscapine, a flavonoid mixture isolated from the dried whole plant of Erigeron breviscapus (Vant.) Hand-Mazz, and valsartan is used as an antihypertensive drug. These two drugs have already been clinically used together to treat diabetic nephropathy (DN) in China, and the combined medications showed some enhanced protection against DN. The aim of this study is to investigate the potential pharmacokinetic interaction between scutellarin and valsartan in rats. Breviscapine injection (20 mg x kg(-1), i.v.) and valsartan (15 mg x kg-, i.g.), either alone or together were given to 18 male Sprague-Dawley rats. Concentrations of scutellarin and valsartan were quantified by HPLC, and pharmacokinetic parameters were calculated by non-compartmental methods. We found that the pharmacokinetic parameters of scutellarin altered significantly after co-administration of oral valsartan. The plasma clearance (CL(p)) and the bile clearance (CL(b)) of scutellarin were reduced significantly in the presence of valsartan. After oral administration of valsartan with or without intravenous scutellarin, however, the pharmacokinetic parameters of valsartan were comparable. In conclusion, our data suggests that the concurrent use of valsartan reduces the biliary excretion of scutellarin, and this may be due to the inhibitory effect of valsartan on the biliary excretion of scutellarin mediated by Mrp2 (Multidrug resistance-associated protein 2).
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Cui
authors.forename: Chong-Chong
authors.initials: CC
authors.lastname: Tian
authors.forename: Ai-Xia
authors.initials: AX
authors.lastname: Ju
authors.forename: Chun-Ting
authors.initials: CT
authors.lastname: Zhang
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Li
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D047310:Apigenin / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D049919:Erigeron / Q000737:chemistry; D005965:Glucuronates / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068756:Valsartan / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000959:Antihypertensive Agents; D047310:Apigenin; D005965:Glucuronates; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000068756:Valsartan; C484876:scutellarin