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Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes

1
BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Korea
2
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(7), 355; https://doi.org/10.3390/pharmaceutics11070355
Received: 24 June 2019 / Revised: 18 July 2019 / Accepted: 19 July 2019 / Published: 22 July 2019
(This article belongs to the Special Issue Drug Metabolism/Transport and Pharmacokinetics)
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Abstract

Catalposide, an active component of Veronica species such as Catalpa ovata and Pseudolysimachion lingifolium, exhibits anti-inflammatory, antinociceptic, anti-oxidant, hepatoprotective, and cytostatic activities. We characterized the in vitro metabolic pathways of catalposide to predict its pharmacokinetics. Catalposide was metabolized to catalposide sulfate (M1), 4-hydroxybenzoic acid (M2), 4-hydroxybenzoic acid glucuronide (M3), and catalposide glucuronide (M4) by human hepatocytes, liver S9 fractions, and intestinal microsomes. M1 formation from catalposide was catalyzed by sulfotransferases (SULTs) 1C4, SULT1A1*1, SULT1A1*2, and SULT1E1. Catalposide glucuronidation to M4 was catalyzed by gastrointestine-specific UDP-glucuronosyltransferases (UGTs) 1A8 and UGT1A10; M4 was not detected after incubation of catalposide with human liver preparations. Hydrolysis of catalposide to M2 was catalyzed by carboxylesterases (CESs) 1 and 2, and M2 was further metabolized to M3 by UGT1A6 and UGT1A9 enzymes. Catalposide was also metabolized in extrahepatic tissues; genetic polymorphisms of the carboxylesterase (CES), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes responsible for catalposide metabolism may cause inter-individual variability in terms of catalposide pharmacokinetics. View Full-Text
Keywords: catalposide; in vitro human metabolism; UDP-glucuronosyltransferase; sulfotransferase; carboxylesterase catalposide; in vitro human metabolism; UDP-glucuronosyltransferase; sulfotransferase; carboxylesterase
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Hwang, D.-K.; Kim, J.-H.; Shin, Y.; Choi, W.-G.; Kim, S.; Cho, Y.-Y.; Lee, J.Y.; Kang, H.C.; Lee, H.S. Identification of Catalposide Metabolites in Human Liver and Intestinal Preparations and Characterization of the Relevant Sulfotransferase, UDP-glucuronosyltransferase, and Carboxylesterase Enzymes. Pharmaceutics 2019, 11, 355.

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