Ursodeoxycholic acid, an inhibitor of hepatocyte nuclear factor 1α, does not increase the systemic exposure of pitavastatin

Hye In Lee, Chang Ik Choi, Joon Ho Sa, Yun Jeong Lee, Jung Woo Bae, Choon Gon Jang, Seok Yong Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Objective: Pitavastatin, a highly potent inhibitor of 3-hydroxy-3-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 (Cmax) 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.

Original languageEnglish
Article numberA7
Pages (from-to)981-985
Number of pages5
JournalInternational Journal of Clinical Pharmacology and Therapeutics
Volume52
Issue number11
DOIs
StatePublished - 1 Nov 2014

Keywords

  • Drug interaction
  • OATP1B1
  • Pharmacokinetics
  • Pitavastatin
  • Ursodeoxycholic acid

Fingerprint

Dive into the research topics of 'Ursodeoxycholic acid, an inhibitor of hepatocyte nuclear factor 1α, does not increase the systemic exposure of pitavastatin'. Together they form a unique fingerprint.

Cite this