Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, Maharashtra, India.
Chem Phys Lipids. 2011 May;164(4):307-13. doi: 10.1016/j.chemphyslip.2011.03.006. Epub 2011 Apr 6.
Prodrug approach using diglyceride as a promoiety is a promising strategy to improve bioavailability of poorly absorbed drugs and the same was explored in the present work to improve oral bioavailability of norfloxacin; a second generation fluoroquinolone antibacterial. The prodrug was synthesized by standard procedures using dipalmitine as a carrier and the structure was confirmed by spectral analysis. Higher LogP indicated improved lipophilicity. The ester linkage between norfloxacin and dipalmitine would be susceptible to hydrolysis by lipases to release the parent drug and carrier in the body. In vivo kinetic studies in rats indicated 53% release of norfloxacin in plasma at the end of 8h. The prodrug exhibited improved pharmacological profile than the parent compound at equimolar dose that indirectly indicated improved bioavailability.
前药策略使用甘油二酯作为前药是提高难吸收药物生物利用度的一种很有前途的策略，本工作探索了将其应用于提高第二代氟喹诺酮类抗菌药诺氟沙星的口服生物利用度。前药通过标准程序合成，使用二棕榈酸作为载体，结构通过光谱分析确认。更高的 LogP 表明改善了亲脂性。诺氟沙星和二棕榈酸之间的酯键在体内易被脂肪酶水解，释放出母体药物和载体。在大鼠体内动力学研究中，8 小时末血浆中释放出 53%的诺氟沙星。与等摩尔剂量的母体化合物相比，前药表现出更好的药理学特性，这间接表明生物利用度得到了提高。
