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

• Published in: Drug design, development and therapy Vol. 16; pp. 3865 - 3876
• Main Authors: Yang, Ling, Shen, Qi, Hu, Chao, Wang, Ying, Zhu, Xiaohong, Shu, Shiqing, Luo, Zhu
• Format: Journal Article
• Language: English
• Published: Macclesfield Dove Medical Press Limited 01.01.2022; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Acids; Aged; Alcohol; Analysis; Antibodies; Bioavailability; Biochemistry; Chromatography; Clinical trials; COX-2 inhibitors; Cyclooxygenase-2; cyclooxygenase-2 inhibitor; Drug dosages; elderly; Electrocardiography; Hematology; Hepatitis; imrecoxib; Inflammation; Laboratories; Metabolism; Metabolites; Older people; Oral administration; Original Research; Osteoarthritis; Pain; Pharmaceuticals; Pharmacokinetics; Pharmacology; Plasma; Safety; Urinalysis; China; United States > US
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S387508

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.sub.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.sub.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 (AU[C.sub.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.sub.max], AU[C.sub.0-t] and AU[C.sub.0-[infinity]] of M0, M1 and M2 between the two groups were not located within 80-125%, indicating [C.sub.max], AU[C.sub.0-t] and AU[C.sub.0-[infinity]] 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