Ursodeoxycholic acid, an inhibitor of hepatocyte nuclear factor 1α, did not increase the systemic exposure of pitavastatin
| Autor: | Seok-Yong Lee, Yun-Jeong Lee, Jung-Woo Bae, Hye-In Lee, Choon-Gon Jang, Chang-Ik Choi, Joon-Ho Sa |
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| Rok vydání: | 2014 |
| Předmět: |
Pharmacology
Male Chemistry Liver-Specific Organic Anion Transporter 1 Ursodeoxycholic Acid Healthy subjects Parallel study Organic Anion Transporters Transporter Reductase Ursodeoxycholic acid Hepatocyte nuclear factors Pharmacokinetics Biochemistry medicine Quinolines Humans Pharmacology (medical) Drug Interactions Hepatocyte Nuclear Factor 1-alpha Hydroxymethylglutaryl-CoA Reductase Inhibitors Pitavastatin medicine.drug |
| Zdroj: | International journal of clinical pharmacology and therapeutics. 52(11) |
| ISSN: | 0946-1965 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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