title: Impact of curcumin on the pharmacokinetics of rosuvastatin in rats and dogs based on the conjugated metabolites.
abstract: 1. Plasma concentrations of curcumin-O-glucuronide (COG) and curcumin-O-sulfate (COS) significantly increased after Sprague-Dawley rats dealt with the Oatp inhibitor rifampicin, with the Cmaxascending 2.9 and 6.7 times, and the AUC0-∞ascending 4.4 and 10.8 times, respectively. When pretreated with the Oat inhibitor probenecid, the Cmaxincreased 4.4 and 20 times, and the AUC0-∞increased 3.2 and 13.9 times, respectively. The results suggested that COG and COS may be the substrates of Oatp and Oat. 2. The accumulation of curcumin significantly increased in organic anion transporting polypeptide (OATP)- and organic anion transporter (OAT)-transfected human embryonic kidney (HEK) 293 systems, which suggested that curcumin was a substrate of OATP1B1, OATP1B3, OATP2B1, OAT1, and OAT3; and COG was a substrate of OATP1B1, OATP1B3, and OAT3. 3. Inhibition study using rosuvastatin as the substrate in OATP1B1- and OATP1B3-transfected cells indicated that curcumin was an OATP1B1 and 1B3 inhibitor, with IC50at 5.19 ± 0.05 and 3.68 ± 0.05 μM, respectively; the data for COG were 1.04 ± 0.01 and 1.08 ± 0.02 μM, respectively. COS was speculated to be an inhibitor of hepatic OATP1B1 as calculated using the ADMET Predictor. 4. COG and COS are substrates and inhibitors of OATP/Oatp. Co-administration of curcumin significantly increased rosuvastatin concentration in rat and dog plasma.
authors.affiliation: a Tongji School of Pharmacy, Huazhong University of Science & Technology , Wuhan , P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: a Tongji School of Pharmacy, Huazhong University of Science & Technology , Wuhan , P.R. China.
authors.forename: Fangrong
authors.initials: F
authors.lastname: Zhang
authors.affiliation: a Tongji School of Pharmacy, Huazhong University of Science & Technology , Wuhan , P.R. China.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.affiliation: b Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , P.R. China , and.
authors.forename: Zitao
authors.initials: Z
authors.lastname: Guo
authors.affiliation: b Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , P.R. China , and.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: b Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , P.R. China , and.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yu
authors.affiliation: c Medical Research Center, Humanwell Healthcare Group Co., Ltd , Wuhan , Hubei , P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: b Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai , P.R. China , and.
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhong
authors.affiliation: a Tongji School of Pharmacy, Huazhong University of Science & Technology , Wuhan , P.R. China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001692:Biological Transport; D003474:Curcumin / Q000378:metabolism*; D004285:Dogs; D004347:Drug Interactions; D057809:HEK293 Cells; D006801:Humans; D027361:Organic Anion Transporters / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068718:Rosuvastatin Calcium / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D000068718:Rosuvastatin Calcium; D003474:Curcumin
keywords: Curcumin; OAT; OATP; drug–drug interaction; rosuvastatin; transporter