title: A Pharmacokinetic/Pharmacodynamic Drug-Drug Interaction Study of Tofogliflozin (a New SGLT2 Inhibitor) and Selected Anti-Type 2 Diabetes Mellitus Drugs.
abstract: OBJECTIVE
  Tofogliflozin is an oral hypoglycemic agent with a novel mechanism of action that reduces blood glucose levels by promoting glucose excretion in urine, achieved by selectively inhibiting sodium-glucose co-transporter 2 (SGLT2). We evaluated the effects of several selected anti-type 2 diabetes mellitus (T2DM) drugs-glimepiride, metformin, sitagliptin, pioglitazone, miglitol, nateglinide, and voglibose-on the pharmacokinetics and pharmacodynamics of tofogliflozin, and the effects of tofogliflozin on the pharmacokinetics of these anti-T2DM drugs in healthy male volunteers.
  
  
  METHODS
  A single dose of either tofogliflozin alone, one of the anti-T2DM drugs alone, or co-administration of tofogliflozin and the anti-T2DM drug was administered to 108 healthy men. Cmax, AUCinf, and cumulative urine glucose excretion after co-administration of tofogliflozin and each of the anti-T2DM drugs was evaluated relative to the values of those parameters after administration of each drug alone.
  
  
  RESULTS
  None of the anti-T2DM drugs had any effect on tofogliflozin exposure. Tofogliflozin had no or little effect on the exposure of any anti-T2DM drug. No anti-T2DM drug had any major effect on the cumulative urine glucose excretion induced by tofogliflozin. There were no safety concerns evident after administration of any drug alone or in co-administration.
  
  
  CONCLUSIONS
  Neither the pharmacokinetics nor the pharmacodynamics of tofogliflozin was affected by any of the anti-T2DM drugs evaluated in this study, nor was the pharmacokinetics of any of the anti-T2DM drugs affected by tofogliflozin in healthy male volunteers.
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kasahara
authors.affiliation: CPC Clinical Trial Hospital, Medipolis Medical Research Institute, Kagoshima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fukase
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohba
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Miyata
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Iida
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takano
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ikeda
authors.affiliation: Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Harigai
authors.affiliation: Clinical Research Planning Department, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Terao
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003510:Cyclohexanes / Q000493:pharmacokinetics / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004347:Drug Interactions; D005947:Glucose / Q000032:analysis; D005960:Glucosides / Q000493:pharmacokinetics* / Q000494:pharmacology*; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008687:Metformin / Q000493:pharmacokinetics / Q000494:pharmacology; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D000077205:Pioglitazone; D000068900:Sitagliptin Phosphate / Q000493:pharmacokinetics / Q000494:pharmacology; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013453:Sulfonylurea Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D045162:Thiazolidinediones / Q000493:pharmacokinetics / Q000494:pharmacology; D014556:Urine / Q000737:chemistry; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D003510:Cyclohexanes; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C045621:miglitol; D017485:1-Deoxynojirimycin; D000077715:Nateglinide; D010649:Phenylalanine; D007294:Inositol; C057619:glimepiride; D008687:Metformin; D005947:Glucose; C575086:6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol; C102817:voglibose; D000068900:Sitagliptin Phosphate; D000077205:Pioglitazone