PMID- 29319909
OWN - NLM
STAT- MEDLINE
DCOM- 20181001
LR  - 20181001
IS  - 1099-081X (Electronic)
IS  - 0142-2782 (Linking)
VI  - 39
IP  - 3
DP  - 2018 Mar
TI  - Inhibitory effects of sulfonylureas and non-steroidal anti-inflammatory drugs on 
      in vitro metabolism of canagliflozin in human liver microsomes.
PG  - 135-142
LID - 10.1002/bdd.2120 [doi]
AB  - Canagliflozin, used to treat type 2 diabetes mellitus (T2DM), is commonly 
      co-administered with sulfonylureas. The objective of the present study was to 
      evaluate the possible inhibitory effect of sulfonylureas and non-steroidal 
      anti-inflammatory drugs (NSAIDs) on canagliflozin metabolism in vitro. Three 
      sulfonylurea derivatives were evaluated as inhibitors: chlorpropamide, 
      glimepiride and gliclazide. Two other NSAIDs were used as positive control 
      inhibitors: niflumic acid and diclofenac. The rate of formation of canagliflozin 
      metabolites was determined by HPLC analysis of in vitro incubations of 
      canagliflozin as a substrate with and without inhibitors, using human liver 
      microsomes (HLMs). Among sulfonylureas, glimepiride showed the most potent 
      inhibitory effect against canagliflozin M7 metabolite formation, with an IC(50) 
      value of 88 mum, compared to chlorpropamide and gliclazide with IC(50) values of 
      more than 500 mum. Diclofenac inhibited M5 metabolite formation more than M7, with 
      IC(50) values of 32 mum for M5 and 80 mum for M7. Niflumic acid showed no 
      inhibition activity against M5 formation, but had relatively selective inhibitory 
      potency against M7 formation, which is catalysed by UGT1A9, with an IC(50) value 
      of 1.9 mum and an inhibition constant value of 0.8 mum. A clinical pharmacokinetic 
      interaction between canagliflozin and sulfonylureas is unlikely. However, a 
      possible clinically important drug interaction between niflumic acid and 
      canagliflozin has been identified.
CI  - Copyright (c) 2018 John Wiley & Sons, Ltd.
FAU - Algeelani, Sara
AU  - Algeelani S
AD  - Graduate Program in Pharmacology and Drug Development, Sackler School of Graduate 
      Biomedical Sciences.
FAU - Alkhelb, Dalal
AU  - Alkhelb D
AD  - Graduate Program in Pharmacology and Drug Development, Sackler School of Graduate 
      Biomedical Sciences.
FAU - Greenblatt, David J
AU  - Greenblatt DJ
AUID- ORCID: 0000-0003-4719-6226
AD  - Graduate Program in Pharmacology and Drug Development, Sackler School of Graduate 
      Biomedical Sciences.
AD  - Tufts University School of Medicine, Boston, MA, 02111, USA.
LA  - eng
PT  - Journal Article
DEP - 20180222
PL  - England
TA  - Biopharm Drug Dispos
JT  - Biopharmaceutics & drug disposition
JID - 7911226
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sulfonylurea Compounds)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 144O8QL0L1 (Diclofenac)
RN  - 4U5MP5IUD8 (Niflumic Acid)
RN  - 6KY687524K (glimepiride)
RN  - G4PX8C4HKV (Gliclazide)
RN  - WTM2C3IL2X (Chlorpropamide)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Canagliflozin/*metabolism/pharmacokinetics
MH  - Chlorpropamide/*pharmacology
MH  - Diclofenac/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Gliclazide/*pharmacology
MH  - Humans
MH  - Hypoglycemic Agents/pharmacology
MH  - Microsomes, Liver/*drug effects/*metabolism
MH  - Niflumic Acid/*pharmacology
MH  - Sulfonylurea Compounds/*pharmacology
OTO - NOTNLM
OT  - IC50
OT  - UGT1A9
OT  - canagliflozin
OT  - glucuronidation
OT  - in vitro metabolism
EDAT- 2018/01/11 06:00
MHDA- 2018/10/03 06:00
CRDT- 2018/01/11 06:00
PHST- 2017/07/20 00:00 [received]
PHST- 2017/11/20 00:00 [revised]
PHST- 2017/12/25 00:00 [accepted]
PHST- 2018/01/11 06:00 [pubmed]
PHST- 2018/10/03 06:00 [medline]
PHST- 2018/01/11 06:00 [entrez]
AID - 10.1002/bdd.2120 [doi]
PST - ppublish
SO  - Biopharm Drug Dispos. 2018 Mar;39(3):135-142. doi: 10.1002/bdd.2120. Epub 2018 
      Feb 22.