Drug Design, Development and Therapy (Feb 2021)
Safety, Tolerability, and Pharmacokinetics of Ibuprofenamine Hydrochloride Spray (NSAIDs), a New Drug for Rheumatoid Arthritis and Osteoarthritis, in Healthy Chinese Subjects
Abstract
Panpan Xie,1 Wei Xue,1 Wenyuan Qi,1 Yang Li,1 Lei Yang,1 Zhaojun Yang,2 Aixin Shi1 1Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Science; Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Beijing, 100730, People’s Republic of China; 2Research and Development Department, Xin Chen Taifei Medical Technology Co. LTD, Tianjin, 300221, People’s Republic of ChinaCorrespondence: Aixin Shi No. 1 Dahua Road, Dongcheng District, Beijing, People’s Republic of ChinaEmail [email protected]: Ibuprofenamine hydrochloride spray is novel transdermal nonsteroidal anti-inflammatory drugs (NSAIDs), under clinical development for the treatment of Rheumatoid Arthritis and Osteoarthritis as a novel transdermal drug.Methods: A single and multiple ascending dose study investigated the safety, tolerability and pharmacokinetics of ibuprofenamine hydrochloride in healthy Chinese subjects. A total of 34 subjects (single-dose study: 34 subjects and multiple-dose study: 20 subjects) were involved in the trial. In the single-dose study, subjects were assigned to one of the four groups received 35, 70, 140, 280 mg. In the 70 mg and 140 mg treatment groups, subjects received one dose on the first day and twice a day from day 6 to 12. The starting dose was determined considering the no observed adverse effect level based on preclinical studies, and the dose escalations in subsequent cohorts were decided based on safety, tolerability, and pharmacokinetic data from previous dose cohorts.Results: After a single dose, both ibuprofenamine and ibuprofen plasma exposure showed a more than dose-proportional increase across a dose range of 35– 280 mg. After multiple dosing, both ibuprofenamine and ibuprofen steady-state exposure increased obviously more than dose-proportional manner across the evaluated dose range (twice a day for 7 days) resulted in obvious accumulation. Single or multiple doses of ibuprofenamine hydrochloride were generally well tolerated and no obvious skin irritation was observed.Conclusion: Ibuprofenamine hydrochloride exhibited a safety and pharmacokinetic profile that supports its future investigation as a potential therapeutic for Rheumatoid Arthritis and Osteoarthritis.Keywords: ibuprofenamine hydrochloride spray, tolerability, safety, pharmacokinetics
