Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the glucuronidation of 3-hydroxydesloratadine
| Autor: | Swapan K. Chowdhury, Yuan Yuan, Ai Duen Iris Su, James E. Patrick, Neil Hapangama, N. Alvarez, Kevin B. Alton, Shmuel Zbaida, Anima Ghosal |
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| Rok vydání: | 2004 |
| Předmět: |
Histamine H1 Antagonists
Non-Sedating Diclofenac Time Factors Bilirubin Metabolite Glucuronidation Pharmaceutical Science Flunitrazepam Pharmacology In Vitro Techniques digestive system chemistry.chemical_compound Glucuronides medicine Humans Pharmacology (medical) Enzyme Inhibitors Glucuronosyltransferase chemistry.chemical_classification Desloratadine General Medicine Loratadine Uridine Enzyme chemistry Biochemistry Microsome Microsomes Liver Glucuronide medicine.drug |
| Zdroj: | Biopharmaceuticsdrug disposition. 25(6) |
| ISSN: | 0142-2782 |
| Popis: | Desloratadine is a non-sedating antihistamine recently approved for the treatment of seasonal allergic rhinitis. The major metabolite of desloratadine in human plasma and urine is the glucuronide conjugate of 3-hydroxydesloratadine. 3-Hydroxydesloratadine-glucuronide is also the major in vitro metabolite of 3-hydroxydesloratadine formed by incubation of 3-hydroxydesloratadine with human liver microsomes supplemented with uridine 5'-diphosphate-glucuronic acid (UDPGA). The metabolite structure was confirmed by LC-MS and LC-MS/MS. Out of ten recombinant human UDP-glucuronosyltransferases (UGTs), UGT1A1, UGT1A3, UGT1A8 and UGT2B15 exhibited catalytic activity with respect to the formation of 3-hydroxydesloratadine-glucuronide. Inhibition studies with known inhibitors of UGT (diclofenac, flunitrazepam and bilirubin) confirmed the involvement of UGT1A1, UGT1A3 and UGT2B15 in the formation of 3-hydroxydesloratadine-glucuronide. The results from this study demonstrated that the in vitro formation of 3-hydroxydesloratadine-glucuronide from 3-hydroxydesloratadine was mediated via UGT1A1, UGT1A3 and UGT2B15 in human liver. |
| Databáze: | OpenAIRE |
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