Yahagi R, Onishi H, Machida Y
Department of Clinical Pharmacy, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo, Japan.
J Control Release. 1999 Aug 27;61(1-2):1-8. doi: 10.1016/s0168-3659(99)00111-x.
In an attempt to restrict drug absorption from suppositories to only the lower rectum, mucoadhesive lidocaine (LID) suppositories were prepared using Witepsol H-15 as a base, and Carbopol 934P (CP) and white beeswax (WAX) as additives. CP has a mucoadhesive property and WAX gives the suppositories stiffness. The suppositories containing 10% CP and 20% WAX stayed in the lower recta of rats for at least 2 h. Double-phased suppositories consisting of a front layer containing 10% CP and 20% WAX and a terminal layer containing LID and various amounts of CP were prepared. In vitro release profiles of LID from double-phased suppositories were similar to conventional single-phased suppositories containing CP alone. Values of AUC(0-6 h) and MRT of LID after administration of double-phased suppositories to rabbits were larger than those for single-phased suppositories with or without CP. On the other hand, the initial plasma metabolites concentrations after administration of double-phased suppositories were significantly lower and tended to exhibit delayed T(max) compared to single-phased suppositories. These results suggest that the double-phased mucoadhesive suppositories suppress initial metabolism of LID, and may be useful for improving bioavailabilities of drugs, like LID, which accept first-pass effect considerably.
为了将栓剂的药物吸收限制在直肠下段，以Witepsol H - 15为基质，卡波姆934P（CP）和白蜂蜡（WAX）为添加剂制备了粘膜粘附性利多卡因（LID）栓剂。CP具有粘膜粘附性，WAX可使栓剂具有硬度。含有10% CP和20% WAX的栓剂在大鼠直肠下段停留至少2小时。制备了双相栓剂，其前层含有10% CP和20% WAX，末端层含有LID和不同量的CP。双相栓剂中LID的体外释放曲线与仅含CP的传统单相栓剂相似。给兔子施用双相栓剂后，LID的AUC(0 - 6 h)和MRT值大于含或不含CP的单相栓剂。另一方面，与单相栓剂相比，施用双相栓剂后的初始血浆代谢物浓度显著较低，且T(max)有延迟趋势。这些结果表明，双相粘膜粘附栓剂可抑制LID的初始代谢，可能有助于提高像LID这样受首过效应影响较大的药物的生物利用度。
