Pharmacodynamics and Pharmacokinetics of a New Type of Compound Lansoprazole Capsule in Gastric Ulcer Rats and Beagle Dogs: Importance of Adjusting Oxidative Stress and Inflammation

Abstract

: The aim of this study was to investigate the pharmacodynamics and pharmacokinetics of a new type of compound lansoprazole capsule in gastric ulcer rats and beagle dogs in order to confirm whether it is more effective in treating gastric ulcers and its rapid absorption. A rat model of gastric ulcers was used to evaluate the anti-ulcerogenic effect of the compound lansoprazole capsule. A fast and sensitive UPLC-MS/MS method was developed to detect lansoprazole in dog plasma. Macroscopic and histological evaluation results revealed that the compound lansoprazole capsule is more effective in treating gastric ulcers as it was able to significantly reduce the gastric ulcer compared to the other groups. Additionally, it was able to enhance the expression of the antioxidant enzyme superoxide dismutase (SOD) and suppress lipid peroxidation as indicated by the reduction of malondialdehyde (MDA) and H+-K+-ATP activity. Furthermore, this capsule increased the expression of mucosal vascular endothelial growth factor (VEGF) and cyclic oxygenase 2 (COX-2). The established UPLC-MS/MS method was successfully applied to the evaluation of pharmacokinetic parameters of lansoprazole in beagle dogs. The results indicate that the compound lansoprazole capsule had an advantage of rapid absorption. This study demonstrated that the compound lansoprazole capsule has better gastroprotective activity and that this might be related to its positive influence on oxidative stress and inflammation. This new type of compound lansoprazole capsule may be potentially useful in preclinical therapy.