Kumari Akriti, Karnatak Manvika, Singh Ajit Shankar, Hassam Mohammad, Rawat Varun, Islam Mohammad Shahidul, Al-Majid Abdullah Mohammed, Singh Mandeep, Verma Ved Prakash
Department of Chemistry, Banasthali University, Banasthali Newai 304022, Rajasthan, India.
Defence Materials and Stores Research Development Establishment, G.T. Road, Kanpur 208013, India.
ACS Omega. 2022 May 17;7(21):17984-17994. doi: 10.1021/acsomega.2c01321. eCollection 2022 May 31.
A mechanistic approach to understand the course of metabolism for synthetic 1,2,4-trioxanes, potent antimalarial compounds, to evaluate their bioavailability for antimalarial action has been studied in the present work. It is an important parameter to study the course of metabolism of a drug candidate molecule when administered via oral route during its journey from oral intake to its target site. From the pharmacokinetics point of view, it determines the bioavailability of an active drug or a prodrug at the target point. In this work, synthetic arylvinyl-1,2,4-trioxanes - have been evaluated under various acidic conditions to mimic the milieu of the stomach (pH between 1.5 and 3.5) through which they have to pass when administered orally. The effect of acid on trioxanes led to their degradation into corresponding ketones and glyoxal. Under such acidic conditions glyoxal polymerized to form a nonisolable condensate product. The study indicates that the actual bioavailability of the drug is far less than the administered dose.
在本研究中，采用了一种机制方法来了解合成的1,2,4 - 三氧杂环己烷（强效抗疟化合物）的代谢过程，以评估它们在抗疟作用中的生物利用度。当候选药物分子通过口服途径从口服摄入到其靶位点的过程中，研究其代谢过程是一个重要参数。从药代动力学的角度来看，它决定了活性药物或前药在靶点的生物利用度。在这项工作中，合成的芳基乙烯基 - 1,2,4 - 三氧杂环己烷在各种酸性条件下进行了评估，以模拟胃的环境（pH值在1.5至3.5之间），口服给药时它们必须通过该环境。酸对三氧杂环己烷的作用导致它们降解为相应的酮和乙二醛。在这种酸性条件下，乙二醛聚合形成一种不可分离的缩合产物。该研究表明，药物的实际生物利用度远低于给药剂量。
