Ogiso T, Ito Y, Iwaki M, Yamamoto Y
Chem Pharm Bull (Tokyo). 1989 Feb;37(2):446-9. doi: 10.1248/cpb.37.446.
A trial transdermal dosage form designed to sustain a suitable plasma concentration of clonazepam (CZP) was produced using a porous membrane (Hipore 2100 or 4050) and applied to rabbits and rats for pharmacokinetic and pharmacodynamic evaluations. The release rate constants for the drug through the porous membranes were significantly smaller than that without any membrane. The transdermal system (Hipore 4050 system, ointment 0.25 g, 2.25 cm2) provided a well sustained plasma concentration of CZP and the therapeutic plasma concentration range was maintained for about 26 h. When the Hipore 4050 system with an increased amount of ointment and enlarged absorption area (0.5 g, 4.0 cm2) was applied, the therapeutic range was sustained for about 40 h, and slightly higher plasma levels over the whole application period and much higher bioavailability (37%) were obtained compared with those after the 2.25 cm2-Hipore 4050 system. The transdermal system exerted an excellent anticonvulsant activity in rats, with the best (3+ or 4+) protective score. The plasma concentrations of CZP when the activity was estimated were in the therapeutic range. Thus, the transdermal system has the potential to be an efficient drug delivery system.
采用多孔膜（Hipore 2100或4050）制备了一种旨在维持氯硝西泮（CZP）适宜血浆浓度的试验性透皮剂型，并将其应用于家兔和大鼠进行药代动力学和药效学评价。药物通过多孔膜的释放速率常数显著小于无任何膜时的释放速率常数。透皮给药系统（Hipore 4050系统，软膏0.25 g，2.25 cm2）能使CZP的血浆浓度得到良好维持，并在约26 h内保持治疗血浆浓度范围。当应用软膏量增加且吸收面积增大（0.5 g，4.0 cm2）的Hipore 4050系统时，治疗范围维持约40 h，与2.25 cm2-Hipore 4050系统相比，在整个给药期间血浆水平略高，生物利用度更高（37%）。该透皮给药系统在大鼠中表现出优异的抗惊厥活性，保护评分最佳（3+或4+）。评估活性时CZP的血浆浓度处于治疗范围内。因此，该透皮给药系统有潜力成为一种高效的药物递送系统。
