Physicochemical, Stress Degradation Evaluation and Pharmacokinetic Study of AZGH101; a New Synthesized COX2 Inhibitor after I.V. and Oral Administration in Male and Female Rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) act mainly via inhibition of prostaglandins synthesis by inhibition of cyclooxygenase (COX) isoenzymes (COX1 and COX 2). Selective COX-2 inhibitors which are also known as coxibs provide the main therapeutic effects of NSAIDs. Zarghi et al. reported 6-benzoyl-2-(4-(methylsulfonyl)phenyl)quinoline-4-carboxylic acid (AZGH 101) as a novel derivative of ketoprofen with improved selectivity index (COX-1/COX-2 inhibitory potency) in comparison with ketoprofen. In this study the log P and stability of AZGH 101 was evaluated and the pharmacokinetic characteristics of this compound were investigated following intravenous (10 mg/kg), and oral administration (20 mg/kg), to Wistar rats. As the data demonstrated the AZGH 101 classified as lipid soluble compound and had suitable stability according to forced degradation protocol ICH guideline for new drug substance. This derivative absorbs, distributes and eliminates similar in both sexes. The AUC 0-∞, absolute bioavailability, Cl and Vd were not different in both sexes. According to the obtained data the AZGH 101 has not a sex dependent pharmacokinetic in Wistar rats.