Percutaneous absorption of clonazepam in rabbit.

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.