Pharmacokinetics, Pharmacodynamics and Safety of Multiple-Infusion Ilaprazole in Healthy Chinese Subjects

Abstract

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.

Efficacy, safety and pharmacokinetics of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control

“…Since the effect of ilaprazole 20 mg was comparable to that of 30 mg, the lower was selected as the loading dose. The following infusion of 10 mg once daily for 2 days was selected because: (i) a previous study indicated that ilaprazole 10 once daily for 5 days provided stable PK and PD, and was well tolerated in healthy subjects; (ii) after receiving a bolus of 20 mg, ilaprazole 10 mg once daily for 2 days was assumed to produce comparable effect to that of 20 mg for 2 days based on a simulation using a mechanism‐based PK/PD model (not published). This was a modified indirect irreversible response model incorporating the circadian rhythm of gastric acid production as well as the effect of food intake .…”

“…The PK, PD and safety of ilaprazole infusion have been investigated in healthy subjects. It was reported that intravenous ilaprazole exhibited dose‐related effect of action and ilaprazole 20 mg provided the most significant pH control effect . However, there are problems remaining unsolved: (i) is 20 mg the right dose producing the best effect; (ii) is there a gap when extrapolating the PK and PD of ilaprazole from healthy subjects to patients; (iii) what is the optimum dose regimen for clinic?…”

“…It was reported that intravenous ilaprazole exhibited dose-related effect of action and ilaprazole 20 mg provided the most significant pH control effect. 16,17 However, there are problems remaining unsolved: (i) is 20 mg the right dose producing the best effect; (ii) is there a gap when extrapolating the PK and PD of ilaprazole from healthy subjects to patients; (iii) what is the optimum dose regimen for clinic? Therefore, the present study was designed to explore the potential PK and PD differences of ilaprazole infusion between healthy subjects and patients, to compare the efficacy of ilaprazole with esomeprazole in healthy subjects and patients with duodenal ulcers, and then determine the optimum dose regimen for Phase 2b/3 studies.…”

Population pharmacokinetic modeling of ilaprazole in healthy subjects and patients with duodenal ulcer in China

“…CTR20150685) clinical trials in healthy subjects, and 1 phase IIa (No. CTR20132846) clinical trial in patients with duodenal ulcer ( Wang et al, 2016a ; Wang et al, 2016b ; Wang et al, 2019 ). All above studies included in this analysis were reviewed and approved by the Institutional Ethics Committee, registered in the China Clinical Trials Registry Center ( chinadrugtrials.org.cn ), and conducted in strict adherence to Good Clinical Practice and the Declaration of Helsinki.…”

Development of a UHPLC-MS/MS method for the quantification of ilaprazole enantiomers in rat plasma and its pharmacokinetic application

“…Additionally, the pharmacokinetics and pharmacodynamics of intravenous ilaprazole in healthy subjects, after single ascending doses, has also been reported [ 9 ]. The pharmacokinetic profile of ilaprazole after 7 days of a 10 mg oral dose, and following 7 consecutive days of a 10 mg intravenous injection, in humans, was also evaluated [ 10 , 11 ].…”