Raloxifene glucuronidation in liver and intestinal microsomes of humans and monkeys: contribution of UGT1A1, UGT1A8 and UGT1A9
| Autor: | Mikio Murata, Manabu Suno, Maho Taguchi, Masato Shigeyama, Naoki Kishi, Akane Takasuka, Takashi Isobe, Nobumitsu Hanioka, Yuki Kokawa |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Adult
medicine.medical_specialty Glucuronosyltransferase Adolescent Health Toxicology and Mutagenesis Glucuronidation Pharmacology Toxicology digestive system 030226 pharmacology & pharmacy Biochemistry Young Adult 03 medical and health sciences Glucuronides 0302 clinical medicine Internal medicine medicine Animals Humans Raloxifene Intestinal Mucosa Aged chemistry.chemical_classification biology Raloxifene Hydrochloride Haplorhini General Medicine Middle Aged Antiestrogen Recombinant Proteins In vitro Intestines Kinetics Enzyme Endocrinology chemistry 030220 oncology & carcinogenesis UDP-Glucuronosyltransferase 1A9 Microsomes Liver biology.protein Microsome medicine.drug |
| Zdroj: | Xenobiotica. 46:289-295 |
| ISSN: | 1366-5928 0049-8254 |
| Popis: | 1. Raloxifene is an antiestrogen that has been marketed for the treatment of osteoporosis, and is metabolized into 6- and 4'-glucuronides by UDP-glucuronosyltransferase (UGT) enzymes. In this study, the in vitro glucuronidation of raloxifene in humans and monkeys was examined using liver and intestinal microsomes and recombinant UGT enzymes (UGT1A1, UGT1A8 and UGT1A9). 2. Although the K(m) and CL(int) values for the 6-glucuronidation of liver and intestinal microsomes were similar between humans and monkeys, and species differences in Vmax values (liver microsomes, humans monkeys; intestinal microsomes, humans monkeys) were observed, no significant differences were noted in the K(m) or S50, Vmax and CL(int) or CLmax values for the 4'-glucuronidation of liver and intestinal microsomes between humans and monkeys. 3. The activities of 6-glucuronidation in recombinant UGT enzymes were UGT1A1 UGT1A8 UGT1A9 for humans, and UGT1A8 UGT1A1 UGT1A9 for monkeys. The activities of 4'-glucuronidation were UGT1A8 UGT1A1 UGT1A9 in humans and monkeys. 4. These results demonstrated that the profiles for the hepatic and intestinal glucuronidation of raloxifene by microsomes were moderately different between humans and monkeys. |
| Databáze: | OpenAIRE |
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