Physicochemical Stress Degradation Evaluation and Pharmacokinetic Study of AZGH102 a New Synthesized COX2 Inhibitors after I.V. and Oral Administration in Male and Female Rats.

摘要

Coxibs such as celecoxib, rofecoxib, and valdecoxib are introduced as selective COX-2 inhibitors to the market. It has been reported that inhibition of COX-2 beside traditional effects of NSAIDs, reduces the risk of colorectal, breast and lung cancers and also slow the progress of Alzheimer’s disease. Zarghi et al. reported 8-benzoyl-2-(4-(methylsulfonyl)phenyl)quinoline-4-carboxylic acid (AZGH 102) as a novel compound with similar IC50 to celecoxib besides improved selectivity index (COX-1/COX-2 inhibitory potency) in comparison with celecoxib. In this study, the physicochemical properties of AZGH 102 such as solubility, log P, and stability were evaluated and the pharmacokinetic characteristics of this compound following intravenous (10 mg/Kg), and oral administration (20 mg/Kg), to male and female Wistar rats were investigated. As the data demonstrated, the AZGH 102 classified as lipophil compound and had suitable stability. This derivative absorbs and distributes faster in female than in male. The AUC 0-∞, absolute bioavailability, Cl and Vd were different in both sexes. According to the obtained data, the AZGH 102 has a sex dependent pharmacokinetic in Wistar rats.