title: Telmisartan increases systemic exposure to rosuvastatin after single and multiple doses, and in vitro studies show telmisartan inhibits ABCG2-mediated transport of rosuvastatin.
abstract: OBJECTIVE
  The ATP-binding cassette transporter G2 (ABCG2) plays an important role in the disposition of rosuvastatin. Telmisartan, a selective angiotension-II type 1 (AT1) receptor blocker, inhibits the transport capacity of ABCG2, which may result in drug interactions. This study investigated the pharmacokinetic interaction between rosuvastatin and telmisartan and the potential mechanism.
  
  
  METHODS
  In this two-phase fixed-order design study, healthy subjects received single doses of 10 mg rosuvastatin at baseline and after telmisartan 40 mg daily for 14 days. Patients with hyperlipidaemia who had been taking rosuvastatin 10 mg daily for at least 4 weeks were given telmisartan 40 mg daily for 14 days together with rosuvastatin. Plasma concentrations of rosuvastatin were measured over 24 h before and after telmisartan administration. In vitro experiments using a bidirectional transport assay were performed to investigate the involvement of ABCG2 in the interaction.
  
  
  RESULTS
  Co-administration of telmisartan significantly increased the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) of rosuvastatin by 71 and 26 %, respectively. The Tmaxvalues were reduced after administration of telmisartan. There was no significant difference in the interaction of rosuvastatin with telmisartan between healthy volunteers and patients receiving long-term rosuvastatin therapy or among subjects with the different ABCG2 421 C>A genotypes. The in vitro experiment demonstrated that telmisartan inhibited ABCG2-mediated efflux of rosuvastatin.
  
  
  CONCLUSIONS
  This study demonstrated that telmisartan significantly increased the systemic exposure to rosuvastatin after single and multiple doses.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.|Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Hon-Kit
authors.initials: HK
authors.lastname: Lee
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Kenneth K W
authors.initials: KK
authors.lastname: To
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Benny S P
authors.initials: BS
authors.lastname: Fok
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Siu-Kwan
authors.initials: SK
authors.lastname: Wo
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Chung-Shun
authors.initials: CS
authors.lastname: Ho
authors.affiliation: Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Chun-Kwok
authors.initials: CK
authors.lastname: Wong
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Thomas Y K
authors.initials: TY
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. btomlinson@cuhk.edu.hk.|Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China. btomlinson@cuhk.edu.hk.
authors.forename: Brian
authors.initials: B
authors.lastname: Tomlinson
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000068718:Rosuvastatin Calcium / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077333:Telmisartan; D044465:White People / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009363:Neoplasm Proteins; D000068718:Rosuvastatin Calcium; D000077333:Telmisartan
keywords: ABCG2; Drug interaction; Rosuvastatin; Telmisartan