Pharmacokinetics and pharmacodynamics of intravenous ilaprazole in healthy subjects after single ascending doses

Abstract

1. Ilaprazole is a novel proton pump inhibitor and this is the first study to investigate the pharmacokinetics, pharmacodynamics and safety of intravenous ilaprazole in healthy volunteers.

2. In this open-label, single-dose, randomized and four-period crossover study, 16 healthy Chinese subjects received ilaprazole 5, 10 or 20 mg intravenously, or 10 mg orally. Serial blood and urine samples were collected and intragastric pH was recorded within 24 h. The percentage time of intragastric pH > 6 was the major index. Safety was assessed throughout the study.

3. Plasma exposure of intravenous ilaprazole increased proportionally over the dose of 5–20 mg. Clearance and volume of distribution were independent of dose. Ilaprazole was not eliminated through urine and the absolute bioavailability was 55.2%. For the intravenous dose of 5, 10, 20 mg, and oral dose of 10 mg, the mean percentages time of intragastric pH > 6 were 47.3%, 52.8%, 68.2% and 47.5%, respectively.

4. Ilaprazole showed linear pharmacokinetics over the dose of 5–20 mg. Intravenous ilaprazole provided rapid onset of action and the potency of effect were exhibited in a dose-dependent manner. Intravenous ilaprazole was safe and well tolerated except for elevated activated partial thromboplastin time (APTT) and prothrombin time (PT).

Keywords:

• Ilaprazole
• intravenous
• pharmacodynamics
• pharmacolinetics
• proton pump inhibitor

Acknowledgements

This study was funded by the National Science and Technology Major Project of China (2012ZX09303006-002) and by Livzon Pharmaceutical Group Inc. (Zhuhai Guangdong, China).

Declaration of interest

Hongyun Wang, Liwei Lang, Pei Hu and Ji Jiang are employes of Peking Union Medical College Hospital. Ning Ou and Ruihua Shi are employes of Jiangsu Province Hospital. The authors report no declarations of interest.