title: Metabolism and disposition of the dipeptidyl peptidase IV inhibitor teneligliptin in humans.
abstract: 1. The absorption, metabolism and excretion of teneligliptin were investigated in healthy male subjects after a single oral dose of 20 mg [(14)C]teneligliptin. 2. Total plasma radioactivity reached the peak concentration at 1.33 h after administration and thereafter disappeared in a biphasic manner. By 216 h after administration, ≥90% of the administered radioactivity was excreted, and the cumulative excretion in the urine and faeces was 45.4% and 46.5%, respectively. 3. The most abundant metabolite in plasma was a thiazolidine-1-oxide derivative (designated as M1), which accounted for 14.7% of the plasma AUC (area under the plasma concentration versus time curve) of the total radioactivity. The major components excreted in urine were teneligliptin and M1, accounting for 14.8% and 17.7% of the dose, respectively, by 120 h, whereas in faeces, teneligliptin was the major component (26.1% of the dose), followed by M1 (4.0%). 4. CYP3A4 and FMO3 are the major enzymes responsible for the metabolism of teneligliptin in humans. 5. This study indicates the involvement of renal excretion and multiple metabolic pathways in the elimination of teneligliptin from the human body. Teneligliptin is unlikely to cause conspicuous drug interactions or changes in its pharmacokinetics patients with renal or hepatic impairment, due to a balance in the elimination pathways.
authors.affiliation: DMPK Research Laboratories, Research Division, Mitsubishi Tanabe Pharma Corporation , Kisarazu, Chiba , Japan .
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Nakamaru
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Ruriko
authors.initials: R
authors.lastname: Ikegawa
authors.forename: Shuji
authors.initials: S
authors.lastname: Kinoshita
authors.forename: Begonya
authors.initials: B
authors.lastname: Perez Madera
authors.forename: Dave
authors.initials: D
authors.lastname: Gunput
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Martin
authors.initials: M
authors.lastname: Davies
authors.forename: Stuart
authors.initials: S
authors.lastname: Mair
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kume
authors.forename: Masayuki
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000042:Absorption; D000328:Adult; D019540:Area Under Curve; D002250:Carbon Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D008954:Models, Biological; D015394:Molecular Structure; D010105:Oxygenases / Q000378:metabolism*; D011720:Pyrazoles / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D012588:Scintillation Counting; D053778:Thiazolidines / Q000097:blood / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: C579035:3-(4-(4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl)pyrrolidin-2-ylcarbonyl)thiazolidine; D002250:Carbon Radioisotopes; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011720:Pyrazoles; D053778:Thiazolidines; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human