PMID- 15334623
OWN - NLM
STAT- MEDLINE
DCOM- 20041222
LR  - 20171116
IS  - 0142-2782 (Print)
IS  - 0142-2782 (Linking)
VI  - 25
IP  - 6
DP  - 2004 Sep
TI  - Identification of human UDP-glucuronosyltransferase enzyme(s) responsible for the 
      glucuronidation of 3-hydroxydesloratadine.
PG  - 243-52
AB  - 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.
FAU - Ghosal, Anima
AU  - Ghosal A
AD  - Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, 
      Kenilworth, New Jersey 07033, USA. anima.ghosal@spcorp.com
FAU - Yuan, Yuan
AU  - Yuan Y
FAU - Hapangama, Neil
AU  - Hapangama N
FAU - Su, Ai Duen Iris
AU  - Su AD
FAU - Alvarez, Narciso
AU  - Alvarez N
FAU - Chowdhury, Swapan K
AU  - Chowdhury SK
FAU - Alton, Kevin B
AU  - Alton KB
FAU - Patrick, James E
AU  - Patrick JE
FAU - Zbaida, Shmuel
AU  - Zbaida S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Biopharm Drug Dispos
JT  - Biopharmaceutics & drug disposition
JID - 7911226
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glucuronides)
RN  - 0 (Histamine H1 Antagonists, Non-Sedating)
RN  - 144O8QL0L1 (Diclofenac)
RN  - 3H9FFN759V (3-hydroxydesloratadine)
RN  - 620X0222FQ (Flunitrazepam)
RN  - 7AJO3BO7QN (Loratadine)
RN  - EC 2.4.1.- (UDP-glucuronosyltransferase, UGT1A3)
RN  - EC 2.4.1.- (UGT1A1 enzyme)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.4.1.17 (UDP-glucuronosyltransferase 2B15, human)
RN  - EC 2.4.1.17 (UDP-glucuronosyltransferase, UGT1A8)
RN  - FVF865388R (desloratadine)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Bilirubin/pharmacology
MH  - Diclofenac/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Flunitrazepam/pharmacology
MH  - Glucuronides/*metabolism
MH  - Glucuronosyltransferase/administration & dosage/antagonists & 
      inhibitors/*metabolism
MH  - Histamine H1 Antagonists, Non-Sedating/*metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Loratadine/*analogs & derivatives/*metabolism
MH  - Microsomes, Liver/enzymology/metabolism
MH  - Time Factors
EDAT- 2004/08/31 05:00
MHDA- 2004/12/23 09:00
CRDT- 2004/08/31 05:00
PHST- 2004/08/31 05:00 [pubmed]
PHST- 2004/12/23 09:00 [medline]
PHST- 2004/08/31 05:00 [entrez]
AID - 10.1002/bdd.405 [doi]
PST - ppublish
SO  - Biopharm Drug Dispos. 2004 Sep;25(6):243-52. doi: 10.1002/bdd.405.