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High-fat diets enhance and delay ursodeoxycholic acid absorption but elevate circulating hydrophobic bile salts. | LitMetric

High-fat diets enhance and delay ursodeoxycholic acid absorption but elevate circulating hydrophobic bile salts.

Front Pharmacol

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, China.

Published: April 2023

Ursodeoxycholic acid (UDCA) is a natural drug essential for the treatment of cholestatic liver diseases. The food effects on the absorption of UDCA and the disposition of circulating bile salts remain unclear despite its widespread global uses. This study aims to investigate the effects of high-fat (HF) diets on the pharmacokinetics of UDCA and disclose how the circulated bile salts were simultaneously perturbed. After an overnight fast, a cohort of 36 healthy subjects received a single oral dose (500 mg) of UDCA capsules, and another cohort of 31 healthy subjects received the same dose after consuming a 900 kcal HF meal. Blood samples were collected from 48 h pre-dose up to 72 h post-dose for pharmacokinetic assessment and bile acid profiling analysis. The HF diets significantly delayed the absorption of UDCA, with the T of UDCA and its major metabolite, glycoursodeoxycholic acid (GUDCA), changing from 3.3 h and 8.0 h in the fasting study to 4.5 h and 10.0 h in the fed study, respectively. The HF diets did not alter the C of UDCA and GUDCA but immediately led to a sharp increase in the plasma levels of endogenous bile salts including those hydrophobic ones. The AUC of UDCA significantly increased from 25.4 μg h/mL in the fasting study to 30.8 μg h/mL in the fed study, while the AUC of GUDCA showed no difference in both studies. As a result, the C of total UDCA (the sum of UDCA, GUDCA, and TUDCA) showed a significant elevation, while the AUC of total UDCA showed a slight increase without significance in the fed study compared to the fasting study. The HF diets delay UDCA absorption due to the extension of gastric empty time. Although UDCA absorption was slightly enhanced by the HF diets, the beneficial effect may be limited in consideration of the simultaneous elevation of circulating hydrophobic bile salts.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10149867PMC
http://dx.doi.org/10.3389/fphar.2023.1168144DOI Listing

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