The Pharmacokinetic Profile of Ursodeoxycholic Acid And Its Metabolites In Healthy Elderly Subjects

[Speaker] Seonghae Yoon:1
[Co-author] Soyoung Lee:2, Jae-Yong Chung:1
1:Seoul National University Bundang Hospital, Korea, 2:Seoul National University College of Medicine and Hospital, Korea

Ursodeoxycholic acid (UDCA) is one of the bile acids component used for the treatment of primary biliary cirrhosis and gallstones. It inhibits absorption of cholesterol and has the cytoprotective and antioxidative effect. The study aims to evaluate the pharmacokinetic (PK) properties of UDCA and its metabolites, glyco-UDCA (G-UDCA) and tauro-UDCA (T-UDCA), in healthy elderly subjects.
A randomized, open-label, two-treatment, one-sequence, multiple-dose, parallel study was conducted. The subjects received either 400 mg or 800 mg of UDCA in day 1 and 200 mg UDCA twice daily for 2-weeks. Blood samples were obtained up to 24 h after the first administration of UDCA in each group. The PK parameters were calculated using a non-compartmental analysis method. Safety was evaluated through vital signs, adverse events, electrocardiograms and clinical laboratory tests.
Sixteen subjects completed the study with no clinically significant safety issues. The time-concentration profile of UDCA, G-UDCA, and T-UDCA are shown in Figure 1. For UDCA 400 and 800 mg dose groups, time to reach the maximum plasma concentrations (Cmax) were 2 h and the Cmax were 2680.75 and 5246.50 ng/mL; the mean area under the concentration time curve (AUClast) were 15741.29 and 29462.52 h*ng/mL, respectively. G-UDCA and T-UDCA showed multiple peaks with the time to reach Cmax ranging 8-10 h. For 400 and 800 mg dose groups, the mean Cmax of G-UDCA were 1536.99 and 2579.13 ng/mL; the mean AUClast of G-UDCA were 17851.37 and 30833.53 h*ng/mL; the mean Cmax of T-UDCA were 60.67 and 101.52 ng/mL; the mean AUClast of T-UDCA were 571.33 and 1042.71 h*ng/mL, respectively.
The UDCA, G-UDCA, and T-UDCA showed multiple peaks due to enteric recirculation. The peak concentration of UDCA was higher compared to G-UDCA, however, the systemic exposure of UDCA was lower than G-UDCA in elderly subjects.

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