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

BACKGROUND: 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 (T(max)) around 2 hours. The concentration–time curves of imrecoxib (M0) showed higher interindividual variability in elderly subjects compared with non-elderly subjects. Peak concentration (C(max)) 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 (AUC(0-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 C(max), AUC(0-t) and AUC(0-∞) of M0, M1 and M2 between the two groups were not located within 80–125%, indicating C(max), AUC(0-t) and AUC(0-∞) 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.