Safety, Tolerability and Pharmacokinetics of Single Ascending and Multiple Oral Doses of Tegoprazan in Healthy Chinese Subjects

• Published in: Clinical drug investigation Vol. 41; no. 1; pp. 89 - 97
• Main Authors: He, Jinjie, Cao, Guoying, Yu, Jicheng, Wang, Jingjing, Cheng, Nengneng, Wu, Jufang, Zhang, Jing, Wu, Xiaojie, Zhang, Basheng, Lu, Jiayan, Chen, Shangzhi
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2021; Springer Nature B.V
• Subjects: Adenosine triphosphatase; Administration, Oral; Adult; Area Under Curve; Asian Continental Ancestry Group; Benzene Derivatives - administration & dosage; Benzene Derivatives - adverse effects; Benzene Derivatives - pharmacokinetics; Blood & organ donations; Chromatography; Chromatography, Liquid; Double-Blind Method; Drug dosages; Electrocardiography; Female; Gastroesophageal reflux; Hepatitis; Humans; Imidazoles - administration & dosage; Imidazoles - adverse effects; Imidazoles - pharmacokinetics; Internal Medicine; Male; Mass spectrometry; Medical laboratories; Medicine; Medicine & Public Health; Original Research Article; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Plasma; Potassium; Scientific imaging; Tandem Mass Spectrometry; Ulcers; Vital signs; Young Adult; China
• ISSN: 1173-2563; 1179-1918; 1179-1918
• DOI: 10.1007/s40261-020-00986-4

Background and Objectives Tegoprazan is one of the potassium-competitive acid blockers (P-CABs). It exhibits its anti-secretory effects by competitively and reversibly blocking the availability of K + of the H + , K + -ATPase. This study was designed to investigate the safety and pharmacokinetics of tegoprazan in healthy Chinese subjects. Methods Thirty-eight healthy Chinese subjects were recruited in this randomized, single-center, double-blind, placebo-controlled study, with a single ascending dose of 50, 100, 200 mg and a multiple dose of 100 mg for 10 days. The plasma concentration of tegoprazan was determined by a validated liquid chromatography tandem mass spectrometry (LC–MS/MS) method. Pharmacokinetics were evaluated via non-compartmental and compartmental model analysis. Safety was assessed by physical examinations, vital signs, clinical laboratory tests, and electrocardiograms. Results No serious adverse event was observed in this study. After single-dose administration (50, 100 and 200 mg), tegoprazan was rapidly absorbed with a median maximum measure plasma concentration ( T max ) at 0.5 h and declined with a terminal (elimination) half-life ( t 1/2 ) of 3.87–4.57 h. The maximum measured plasma concentration ( C max ) for tegoprazan was 813.80, 1494.60 and 2829.00 ng/mL. Meanwhile, the corresponding area under the concentration–time curve (AUC) from time zero to infinity (AUC 0−inf ) was 2761.00, 5980.05 and 11,044.72 ng∙h/mL in 50, 100, 200 mg group, respectively. Dose-dependent increase was observed in the value of C max and AUC after administration of tegoprazan 50 to 200 mg. The two-compartment model well described the pharmacokinetic profile of tegoprazan. In the steady state, no accumulation was found after repeated administration at the 100-mg dose level. No experimental differences were found based on gender. Conclusions Tegoprazan was well tolerated in the dose range of 50–200 mg in single- and 100 mg in multiple-dose studies. Tegoprazan shows dose linearity with oral administration after a single dose of 50 to 200 mg and less drug accumulation after 10 days of continuous administration in 100 mg.