塞来昔布
医学
药理学
曲马多
不利影响
止痛药
药代动力学
作者
Neus Gascón,Carmen Almansa,Manuel Merlos,José Miguel Vela,Gregorio Encina,Adelaida Morte,Kevin J. Smith,Carlos R. Plata‐Salamán
标识
DOI:10.1080/13543784.2019.1612557
摘要
Introduction: Pain management is a major unmet need due to the suboptimal efficacy and undesirable side effects of current analgesics. Multimodal therapies recruiting complementary mechanisms of action may help address this. Co-crystals incorporating two active pharmaceutical ingredients (APIs) constitute an innovative approach to multimodal therapy, particularly if modification of the physicochemical properties of constituent APIs can be translated into clinical benefits.Areas covered: The preclinical and clinical profiles of Co-Crystal of Tramadol-Celecoxib (CTC), a novel API–API co-crystal (1:1 molecular ratio of rac-tramadol.hydrochloride and celecoxib) are described.Expert opinion: CTC may provide a relevant addition to pain therapy due to its: i) unique co-crystal structure conferring differentiated intrinsic dissolution profiles on constituent APIs, ii) modified clinical pharmacokinetics (slower absorption of tramadol and faster absorption of celecoxib) compared with commercially available single-entity reference products (in agreement with modified dissolution rates), iii) superior benefit–risk ratio compared with reference products (suggested by preclinical synergistic antinociceptive effects, without potentiation of adverse effects), and iv) efficacy in a phase 2 trial of moderate to severe pain following extraction of ≥2 impacted third molars requiring bone removal, where CTC doses containing low doses of APIs exerted a significant effect. Phase 3 studies are currently ongoing.
科研通智能强力驱动
Strongly Powered by AbleSci AI