title: Evaluation of drug efficacy of DPP-4 inhibitors based on theoretical analysis with pharmacokinetics and pharmacodynamics.
abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors are used clinically as therapeutic agents for the treatment of diabetes. To determine the rate of DPP-4 inhibition induced by these inhibitors, pharmacokinetic and pharmacodynamic parameters were used to theoretically examine the relationship between the rate of DPP-4 inhibition and clinical efficacy following the administration of four different DPP-4 inhibitors (sitagliptin, vildagliptin, alogliptin, linagliptin) by focusing on the increase in the level of glucagon-like peptide-1 (GLP-1) induced by their administration. On the basis of the relationship shown, changes in clinical efficacy in association with dose change were examined in order to discuss clinical dosage from the standpoint of proper usage. The results indicate that a high rate of DPP-4 inhibition is necessary for the onset of the effect of an administered the DPP-4 inhibitor and that the average value for the DPP-4 inhibition rate can be utilized as a common parameter of clinical efficacy. Furthermore, the efficacy profiles of the present DPP-4 inhibitors could be demonstrated on the basis of an increase in the GLP-1 level. It is considered that the present findings provide useful information for promoting the proper clinical use of DPP-4 inhibitors. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Takayanagi
authors.affiliation: Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Koji
authors.identifier: http://orcid.org/0000-0002-0425-0205
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000465:Algorithms; D019540:Area Under Curve; D003920:Diabetes Mellitus / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D009570:Nitriles / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D011759:Pyrrolidines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014498:Uracil / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000077597:Vildagliptin
chemical_list: D000218:Adamantane; D054873:Dipeptidyl-Peptidase IV Inhibitors; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D009570:Nitriles; D010880:Piperidines; D011759:Pyrrolidines; D014498:Uracil; D000077597:Vildagliptin; C520853:alogliptin
keywords: DPP-4 inhibitors; pharmacodynamics; pharmacokinetics; proper usage; theoretical analysis