title: Pharmacokinetic Drug-Drug Interactions Between Vonoprazan and Low-Dose Aspirin or Nonsteroidal Anti-inflammatory Drugs: A Phase 2, Open-Label, Study in Healthy Japanese Men.
abstract: BACKGROUND
  Gastroprotective agents are recommended for patients receiving low-dose aspirin (LDA) or nonsteroidal anti-inflammatory drugs (NSAIDs). Vonoprazan is a potassium-competitive acid blocker recently approved for the prevention of peptic ulcer recurrence in patients receiving LDA or NSAIDs.
  
  
  METHODS
  This phase 2, open-label, single-center study in healthy Japanese males evaluated drug-drug interactions between vonoprazan 40 mg and LDA (100 mg) or NSAIDs [loxoprofen sodium (60 mg), diclofenac sodium (25 mg), or meloxicam (10 mg)] and vice versa. Subjects were allocated to one of eight cohorts and received their orally administered treatment regimen (to assess the effect of vonoprazan vs. NSAID or LDA, or vice versa) once daily. Endpoints were the pharmacokinetics of plasma concentrations of the study drugs alone and in combination (primary), safety (secondary), and vonoprazan effects on aspirin-mediated inhibition of platelet-aggregation.
  
  
  RESULTS
  Of 109 subjects screened, 64 were assigned to one of eight cohorts (n = 8 per cohort) and received treatment, one subject discontinued due to a treatment-emergent adverse event (TEAE), and 63 completed the study. There were few differences in the pharmacokinetics of vonoprazan when administered with LDA or NSAIDs, and few differences in the pharmacokinetics of LDA or NSAIDs when administered with vonoprazan. The differences were small and not clinically meaningful. Inhibition of arachidonic-induced platelet aggregation by LDA was not influenced by vonoprazan. Six patients experienced a TEAE, all were mild and were deemed unrelated to study drugs. One subject withdrew due to infection (tonsillitis).
  
  
  CONCLUSIONS
  No clinically meaningful drug-drug interactions were observed and vonoprazan was well tolerated when administered with LDA or NSAIDs.
  
  
  BACKGROUND
  JapicCTI-153100.
authors: Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan. yuuichi.sakurai@takeda.com.
authors: Yuuichi
authors: Y
authors: Sakurai
authors: Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan.
authors: Madoka
authors: M
authors: Shiino
authors: Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan.
authors: Sayako
authors: S
authors: Horii
authors: Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan.
authors: Hiroyuki
authors: H
authors: Okamoto
authors: Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan.
authors: Koki
authors: K
authors: Nakamura
authors: Takeda Pharmaceutical Company Ltd., 1-1, Doshomachi 4-Chome, Chuo-ku, Osaka, 540-8645, Japan.
authors: Akira
authors: A
authors: Nishimura
authors: SOUSEIKAI Hakata Clinic, Fukuoka, Japan.
authors: Yukikuni
authors: Y
authors: Sakata
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019540:Area Under Curve; D001241:Aspirin / Q000494:pharmacology*; D018592:Cross-Over Studies; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000493:pharmacokinetics*; D011758:Pyrroles / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000493:pharmacokinetics*
chemical_list: C552956:1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054328:Proton Pump Inhibitors; D011758:Pyrroles; D013449:Sulfonamides; D001241:Aspirin