Ogiso T, Ito Y, Iwaki M, Yamamoto Y
Chem Pharm Bull (Tokyo). 1989 Feb;37(2):442-5. doi: 10.1248/cpb.37.442.
The percutaneous (p.c.) absorption of clonazepam (CZP), an antiepileptic drug, was investigated in rabbits. CZP was efficiently absorbed from a gel ointment (0.5% CZP, 1g, 9 cm2) with Azone and therapeutic plasma concentrations were maintained for 27 h. The bioavailability of CZP from the gel ointment was 47.2 +/- 3.1%, which was significantly larger than that (3.3 +/- 0.5%) after the ointment without Azone or that (12.5 +/- 3.6%) after oral administration. About a half of CZP in the ointment with Azone was absorbed during a 24 h application. The maximum and minimum plasma concentrations and the area under the plasma concentration-time curve gradually increased during repeated application of the ointment (2% CZP, 0.25 g/d, 2.25 cm2), probably due to the accumulation of drug in the skin and body. The efficient absorption and sustained plasma concentration of CZP after application suggest that a once a day p.c. administration regimen is possible by using the ointment with Azone.
在兔体内研究了抗癫痫药物氯硝西泮（CZP）的经皮（p.c.）吸收情况。CZP能从含氮酮的凝胶软膏（0.5% CZP，1g，9 cm²）中有效吸收，且治疗性血浆浓度可维持27小时。凝胶软膏中CZP的生物利用度为47.2±3.1%，显著高于不含氮酮的软膏（3.3±0.5%）或口服给药后（12.5±3.6%）的生物利用度。在24小时的涂抹过程中，含氮酮软膏中约一半的CZP被吸收。在重复涂抹软膏（2% CZP，0.25 g/d，2.25 cm²）期间，血浆最大和最小浓度以及血浆浓度-时间曲线下面积逐渐增加，这可能是由于药物在皮肤和体内蓄积所致。涂抹后CZP的有效吸收和持续的血浆浓度表明，使用含氮酮的软膏每天经皮给药一次的方案是可行的。
