Phase I Study to Evaluate the Effect of Hepatic Impairment on Pharmacokinetics and Safety of Tegoprazan, a Potassium Competitive Acid Blocker.

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Tác giả: Deborah Kang, Anhye Kim, In Hee Kim, Jungryul Kim, Yang Won Min, Youlim Seo, Dongseong Shin

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: United States : Advances in therapy , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 55158

INTRODUCTION: Tegoprazan is a potassium-competitive acid blocker, and its systemic exposure is presumably affected by hepatic clearance and bioavailability. This study aimed to investigate the effect of hepatic impairment (HI) on the safety and pharmacokinetics of tegoprazan and metabolite. METHODS: An open-label, multicenter, parallel-group study was conducted in patients with mild (n = 8), moderate (n = 8) and severe (n = 1) HI according to the Child-Pugh classification as well as controls. Healthy subjects (n = 8) were matched to patients with the moderate category based on age, body mass index and sex. Blood and urine samples were obtained to evaluate the concentrations of tegoprazan and metabolite (M1) until 48 h after a single oral administration of 50 mg of tegoprazan. RESULTS: The geometric mean ratio with a 90% confidence interval of maximum plasma concentration and area under the plasma concentration-time curve for tegoprazan in patients with impaired hepatic function compared to controls were 0.8228 (0.4997-1.3550) and 1.2264 (0.7447-2.0197) in the mild category, 1.0332 (0.6274-1.7015) and 1.7676 (1.0733-2.9109) in the moderate category, and 1.0699 (0.3713-3.0823) and 1.9567 (0.6792-5.6377) in the severe category. The half-life, apparent clearance, renal clearance, and fraction unbound to plasma protein were comparable across study groups. The plasma concentration of M1 increased and decreased faster in the normal group. Tegoprazan was generally well tolerated in patients with HI. CONCLUSIONS: Systemic exposure to tegoprazan tended to be increased in subjects with HI. The difference between patients with mild HI and the controls was deemed not to require dose adjustment for tegoprazan. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT04494269 (31 Jul 2020).
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