title: Ursodeoxycholic acid, an inhibitor of hepatocyte nuclear factor 1α, did not increase the systemic exposure of pitavastatin.
abstract: OBJECTIVE
  Pitavastatin, a highly potent inhibitor of 3-hydroxy-methylglutarylcoenzyme A reductase, is a known substrate of OATP1B1. Ursodeoxycholic acid (UDCA) inhibits OATP1B1 expression by repressing hepatocyte nuclear factor 1α (HNF1α). Thus, the effects of UDCA on the pharmacokinetics of pitavastatin were investigated in healthy subjects.
  
  
  METHODS
  An open-label, 2-phase, parallel study was conducted with 13 healthy volunteers. In the control phase, after an overnight fast, each subject received a single dose of 2 mg pitavastatin. After a 1-week washout period, in the UDCA phase, subjects received a daily oral dose of 600 mg of UDCA (300 mg b.i.d.) for 14 days. On day 15, 2 mg of pitavastatin was administered as described previously for the control phase.
  
  
  RESULTS
  In the UDCA phase, the maximum plasma concentration (C(max)) of pitavastatin was slightly higher than in the control phase (48.6 ± 22.9 ng/mL vs. 42.4 ± 16.1 ng/mL). However, the overall pharmacokinetic parameters of pitavastatin and pitavastatin lactone during the two study phases were not significantly different.
  
  
  CONCLUSIONS
  UDCA had no significant effect on the pharmacokinetics of pitavastatin. These results do not support the notion that UDCA increases the systemic exposure of OATP1B1 substrate by inhibiting HNF1α and decreasing OATP1B1 transporter expression.
authors.forename: Hye-In
authors.initials: HI
authors.lastname: Lee
authors.forename: Chang-Ik
authors.initials: CI
authors.lastname: Choi
authors.forename: Joon-Ho
authors.initials: JH
authors.lastname: Sa
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jung-Woo
authors.initials: JW
authors.lastname: Bae
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
mesh_terms: D004347:Drug Interactions; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000037:antagonists & inhibitors*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000502:physiology; D011804:Quinolines / Q000493:pharmacokinetics*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011804:Quinolines; C503999:SLCO1B1 protein, human; D014580:Ursodeoxycholic Acid; C108475:pitavastatin