The pharmacokinetics, pharmacodynamics and safety of oral doses of ilaprazole 10, 20 and 40 mg and esomeprazole 40 mg in healthy subjects: a randomised, open‐label crossover study

• Published in: Alimentary pharmacology & therapeutics Vol. 40; no. 5; pp. 548 - 561
• Main Authors: Shin, J. S., Lee, J. Y., Cho, K. H., Park, H. L., Kukulka, M., Wu, J.‐T., Kim, D. Y., Park, S.‐H.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell 01.09.2014
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles - administration & dosage; 2-Pyridinylmethylsulfinylbenzimidazoles - adverse effects; 2-Pyridinylmethylsulfinylbenzimidazoles - blood; 2-Pyridinylmethylsulfinylbenzimidazoles - pharmacokinetics; Administration, Oral; Adult; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - adverse effects; Anti-Ulcer Agents - blood; Anti-Ulcer Agents - pharmacokinetics; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Cross-Over Studies; Esomeprazole - administration & dosage; Esomeprazole - adverse effects; Esomeprazole - blood; Esomeprazole - pharmacokinetics; Female; Gastrins - blood; Healthy Volunteers; Humans; Hydrogen-Ion Concentration; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - adverse effects; Proton Pump Inhibitors - blood; Proton Pump Inhibitors - pharmacokinetics; Human; Pharmacokinetic pharmacodynamic relationship; Healthy subject; Enzyme; Toxicity; Oral administration; H; Enzyme inhibitor; Antiulcer agent; K; Crossover study; Proton pump inhibitor; Randomization; Benzimidazole derivatives; Antisecretory agent; Esomeprazole; exchanging ATPase; Hydrolases; Ilaprazole; Pharmacokinetics; Dose
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.12860

Summary Background Ilaprazole, a proton pump inhibitor (PPI) currently in clinical use, may provide improved acid suppression vs. other PPIs. Aim To compare the pharmacodynamic and pharmacokinetic profiles of ilaprazole and esomeprazole. Methods A phase 1, randomised, open‐label, single‐centre, 4‐period crossover study was conducted in 40 healthy volunteers. Ilaprazole 10, 20 or 40 mg or esomeprazole 40 mg was administered once daily for 5 days with ≥5‐day washout intervals. Pharmacokinetic blood samples and intragastric pH measurements were collected at scheduled timepoints for 24 h after dosing on Days 1 and 5. Results Esomeprazole 40 mg provided significantly better pH control during the initial hours (0–4 h) after a single dose, but ilaprazole (particularly 20 and 40 mg) provided significantly better pH control for the entire 24‐h period and during evening and overnight hours after single and multiple doses. Increasing ilaprazole doses resulted in dose‐proportional increases in peak plasma concentration and area under the plasma concentration vs. time curve following single and multiple doses. Ilaprazole was safe and generally well tolerated; an unexpectedly high incidence of allergic eye and skin reactions were observed but were not specific to any dosing regimen. Plasma gastrin concentrations did not increase proportionately with increasing ilaprazole dose. Conclusions Ilaprazole provided significantly better pH control over 24 h and during evening and overnight hours compared with esomeprazole in healthy volunteers, which may translate to greater relief of night‐time heartburn in the clinical setting for patients with gastric acid‐related disorders.