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

• Main Authors: Deok-Kyu Hwang (Author), Ju-Hyun Kim (Author), Yongho Shin (Author), Won-Gu Choi (Author), Sunjoo Kim (Author), Yong-Yeon Cho (Author), Joo Young Lee (Author), Han Chang Kang (Author), Hye Suk Lee (Author)
• Format: Book
• Published: MDPI AG, 2019-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Catalposide, an active component of <i>Veronica</i> species such as <i>Catalpa ovata</i> and <i>Pseudolysimachion lingifolium</i>, 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.

Item Description

1999-4923
10.3390/pharmaceutics11070355