title: Disposition and metabolism of TAK-438 (vonoprazan fumarate), a novel potassium-competitive acid blocker, in rats and dogs.
abstract: 1. Following oral administration of [14C]TAK-438, the radioactivity was rapidly absorbed in rats and dogs. The apparent absorption of the radioactivity was high in both species. 2. After oral administration of [14C]TAK-438 to rats, the radioactivity in most tissues reached the maximum at 1-hour post-dose. By 168-hour post-dose, the concentrations of the radioactivity were at very low levels in nearly all the tissues. In addition, TAK-438F was the major component in the stomach, whereas TAK-438F was the minor component in the plasma and other tissues. High accumulation of TAK-438F in the stomach was observed after oral and intravenous administration. 3. TAK-438F was a minor component in the plasma and excreta in both species. Its oxidative metabolite (M-I) and the glucuronide of a secondary metabolite formed by non-oxidative metabolism of M-I (M-II-G) were the major components in the rat and dog plasma, respectively. The glucuronide of M-I (M-I-G) and M-II-G were the major components in the rat bile and dog urine, respectively, and most components in feces were other unidentified metabolites. 4. The administered radioactive dose was almost completely recovered. The major route of excretion of the drug-derived radioactivity was via the feces in rats and urine in dogs.
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kogame
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nonaka
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Yamasaki
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Kawaguchi
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Bernards
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tagawa
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Morohashi
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kondo
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Moriwaki
authors.affiliation: a Drug Metabolism and Pharmacokinetics Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited , Kanagawa , Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Asahi
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D004285:Dogs; D005243:Feces; D054328:Proton Pump Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics; D011758:Pyrroles / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D013449:Sulfonamides / Q000378:metabolism* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D054328:Proton Pump Inhibitors; D011758:Pyrroles; D013449:Sulfonamides
keywords: LC/MS; metabolite profiling; pharmacokinetics; potassium-competitive acid blocker