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Background and Objectives: Ilaprazole is a novel proton pump inhibitor that provides effective and long lasting inhibition of intragastric acid secretion. The objectives of this study were to investigate the pharmacokinetics, pharmacodynamics, and safety of intravenous ilaprazole after multiple administrations in healthy Chinese subjects. Methods: This was an open-label and multiple-dose clinical study. Ten healthy Chinese subjects received 10 mg ilaprazole infusion once daily for 5 days. Helicobacter pylori status was examined. Blood samples were collected and intragastric pH was recorded for 24 h. Safety was assessed throughout the study. Results: There was no accumulation after multiple administrations. The mean steady-state half-life and clearance were comparable to those following single administration. Ilaprazole provided sustainable and significant intragastric pH control in terms of percentage time at pH >4, pH >6 within 24 h and mean 24-h pH values. The pH value within 24 h was affected by Helicobacter pylori infection in subjects with continuous infusion. Intravenous ilaprazole was safe and there were no serious adverse events. Conclusion: Intravenous ilaprazole provided stable pharmacokinetics and pharmacodynamics at a dose of 10 mg once daily for 5 days, and was well tolerated in healthy subjects. [ABSTRACT FROM AUTHOR]

Background and Objective: Tylerdipine hydrochloride (KBP-5660) is a novel L/T-type dual calcium channel blocker developed for the treatment of hypertension. We aimed to study the pharmacokinetics, safety and tolerability of tylerdipine in healthy Chinese subjects.Methods: Two double-blind, randomized, dose-escalation studies were conducted that included a total of 88 healthy subjects: (1) a single-ascending dose (SAD) study; and (2) a multiple-ascending dose (MAD) study. In the SAD study, 64 subjects were randomly assigned to receive a single dose of 0.5, 2.5, 5, 10, 15, 20, 25, or 30 mg of tylerdipine or placebo. In the MAD study, 24 subjects were randomly assigned to receive 10 or 20 mg of tylerdipine or placebo once daily for 9 days. Blood samples were collected at the designated time points for pharmacokinetic analyses. Safety assessments were conducted throughout the study.Results: Following a single oral dose of tylerdipine of 5-30 mg, the mean maximum plasma concentration (Cmax) increased from 0.9993 to 10.11 ng/ml; mean area under the plasma-concentration curve (AUC) from time zero to 72 h increased from 4.332 to 73.95 h·ng/ml. AUC increased in a greater than dose-proportional manner, whereas Cmax exhibited a rough but non-typical dose-proportionality increase. In the MAD study, steady-state conditions were achieved after 1 week of daily dosing in both dose groups. Accumulation of tylerdipine was low, with accumulation ratios (RAUC) of less than 1.65. All adverse events were assessed as mild or moderate.Conclusion: Tylerdipine hydrochloride was safe and well tolerated. The exposure (AUC) of tylerdipine over the dose range of 5-30 mg increased in a greater than dose-proportional manner, while Cmax exhibited a rough but non-typical dose proportionality increase. A slight accumulation of tylerdipine was observed following multiple dosing.Study registrations: CTR20140862 and CTR20150660. [ABSTRACT FROM AUTHOR]