Blanco M D, Trigo R M, Teijón C, Gómez C, Teijón J M
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Biomaterials. 1998 Apr-May;19(7-9):861-9. doi: 10.1016/s0142-9612(97)00247-0.
The release of cytarabine (ara-C) from poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-N-vinyl-2pyrrolidone) hydrogels cross-linked with different amounts of ethyleneglycol dimethacrylate (EGDMA) 'in vivo' has been studied. Two ara-C loaded hydrogel discs, each with 25 mg of the drug, were subcutaneously implanted in the back of male Wistar rats. Total ara-C dose was 230 mg kg(-1). Ara-C and ara-U plasmatic concentration were determined by HPLC. Periods of constant drug concentration are observed from all gels. Ara-C concentrations in the steady-state are between 19.0 +/- 2.0 and 2.2 +/- 0.8 micromol l(-1). The release time of ara-C was between 3 days from pH EMA 0.5% and 16 days from H80/VP20/E15 gels. These results are very different of that obtained when ara-C is administered by intraperitoneal injection, in this case peaks of maximum concentration (between 24 +/- 1 and 3.9 +/- 0.4 microg ml(-1)) 30 min after the injection are originated, and no drug is detected 4 h after the injection.
研究了与不同量的乙二醇二甲基丙烯酸酯(EGDMA)交联的聚(甲基丙烯酸2-羟乙酯)和聚(甲基丙烯酸2-羟乙酯-co-N-乙烯基-2-吡咯烷酮)水凝胶在“体内”阿糖胞苷(ara-C)的释放情况。将两个载有ara-C的水凝胶圆盘,每个圆盘含25mg药物,皮下植入雄性Wistar大鼠背部。ara-C的总剂量为230mg kg(-1)。通过高效液相色谱法测定ara-C和ara-U的血浆浓度。从所有凝胶中都观察到了药物浓度恒定的时期。ara-C在稳态下的浓度在19.0±2.0至2.2±0.8微摩尔/升之间。ara-C的释放时间在pH EMA 0.5%的凝胶为3天至H80/VP20/E15凝胶为16天之间。这些结果与腹腔注射ara-C时获得的结果非常不同,在这种情况下,注射后30分钟会出现最大浓度峰值(在24±1至3.9±0.4微克/毫升之间),注射后4小时未检测到药物。