Luengo Javiana, Aránguiz Teobaldo, Sepúlveda Jacqueline, Hernández Luis, Von Plessing Carlos
Department of Pharmacy, Faculty of Pharmacy, Casilla 237, Universidad de Concepción, Concepción, Chile.
J Pharm Sci. 2002 Dec;91(12):2593-8. doi: 10.1002/jps.10245.
Acyclovir has absorption problems, because of its low solubility and/or its saturable absorption mechanism, that take place in the small intestine in a passive, variable, and incomplete manner. The oral bioavailability of acyclovir is thereby affected and reaches only 15-30%. The purpose of this study was to investigate the possibility of increasing the oral availability of acyclovir by forming inclusion complexes of acyclovir with beta-cyclodextrin. Acyclovir, its complex (1:1) with beta-cyclodextrin (acyclovir-beta-cyclodextrin complex), and a 50:50 mixture of acyclovir and the inclusion complex (acyclovir/complex mixture) as an aqueous suspension were administered intraintestinally to male Sprague-Dawley rats in doses equivalent to an acyclovir dose of 75 mg/kg. Sequential samples of plasma were taken by microdialysis. The samples were analyzed by high-performance liquid chromatography with ultraviolet detection. Plasma concentration versus time curves show that the complex and the mixture of acyclovir/complex have a higher bioavailability and a pharmacokinetic profile than that of the drug itself.
阿昔洛韦存在吸收问题，因其溶解度低和/或存在可饱和吸收机制，这些问题在小肠以被动、可变且不完全的方式发生。阿昔洛韦的口服生物利用度因此受到影响，仅达到15% - 30%。本研究的目的是通过形成阿昔洛韦与β - 环糊精的包合物来研究提高阿昔洛韦口服利用率的可能性。将阿昔洛韦、其与β - 环糊精的复合物（1:1）（阿昔洛韦 - β - 环糊精复合物）以及阿昔洛韦与包合物的50:50混合物（阿昔洛韦/复合物混合物）作为水悬浮液以相当于75 mg/kg阿昔洛韦剂量的剂量经肠道给予雄性斯普拉格 - 道利大鼠。通过微透析采集连续的血浆样本。采用带紫外检测的高效液相色谱法对样本进行分析。血浆浓度 - 时间曲线表明，复合物以及阿昔洛韦/复合物混合物的生物利用度和药代动力学特征均高于药物本身。
