Comparative Pharmacokinetics and Safety of Imrecoxib, a Novel Selective Cyclooxygenase-2 Inhibitor, in Elderly Healthy Subjects

Ling Yang *, Qi Shen *, Chao Hu, Ying Wang, Xiaohong Zhu, Shiqing Shu, Zhu Luo Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhu Luo, Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital Sichuan University, No. 37 Guoxue Lane, Chengdu, Sichuan, 610044, People’s Republic of China, Tel +86 28 85422707, Email luozhu720@163.comBackground: Imrecoxib is a novel and moderately selective cyclooxygenase-2 inhibitor with properties of anti-inflammation and alleviating pain, which is widely applied in osteoarthritis patients. The pharmacokinetic data supporting imrecoxib’s rational use in elderly population are not available.Purpose: The study aims to investigate the pharmacokinetics of imrecoxib and its main metabolites and explore the safety of imrecoxib in elderly healthy subjects.Methods: A total of 19 healthy subjects including 10 non-elderly and 9 elderly subjects received single dose of 100 mg imrecoxib under fasting condition. Pharmacokinetics, safety and tolerability profiles were assessed.Results: After oral administration of single dose of 100 mg imrecoxib, it was absorbed into plasma with median time to reach peak concentration (Tmax) around 2 hours. The concentration–time curves of imrecoxib (M0) showed higher interindividual variability in elderly subjects compared with non-elderly subjects. Peak concentration (Cmax) of M0, its hydroxyl metabolite M1 and carboxylated metabolite M2 in plasma increased by 39%, 21% and 17%, and area under concentration–time curve from time 0 to time t (AUC0-t) of M0, M1 and M2 in plasma increased by 34%, 13% and 27%, respectively, in elderly subjects compared with non-elderly subjects. The 90% CIs of geometric mean ratios of Cmax, AUC0-t and AUC0-∞ of M0, M1 and M2 between the two groups were not located within 80– 125%, indicating Cmax, AUC0-t and AUC0-∞ were not completely equivalent between non-elderly and elderly healthy subjects. However, comparison of pharmacokinetic data of M0, M1 and M2 between the two groups showed no significant difference (P> 0.05). Imrecoxib was well tolerated in both non-elderly and elderly healthy subjects, especially with favorable gastrointestinal and cardiovascular safety profiles.Conclusion: Pharmacokinetic and safety profiles of imrecoxib in elderly healthy subjects indicated that no dose adjustment should be required for elderly population.Keywords: cyclooxygenase-2 inhibitor, imrecoxib, pharmacokinetics, safety, elderly