Abstract
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, 9cm2) with Azone[○!R] and therapeutic plasma concentrations were maintained for 27h. 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[○!R] or that (12.5±3.6%) after oral administration. About a half of CZP in the ointment with Azone[○!R] 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, 2.25cm2), 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[○!R].
