The percutaneous absorption of propranolol and prediction of the plasma concentration.

Abstract

In order to avoid first-pass metabolism and to maintain therapeutically effective concentration of propranolol (PL) for a prolonged time, ointments of PL were prepared and the percutaneous (p.c.) absorption was investigated in rabbits. To describe the plasma PL concentration profile during repeated p.c. administrations, a simple pharmacokinetic model, including a first-order absorption process, was applied. The p.c. absorption of PL from both macrogol (400:4000, 30:40, g/g) and Carbopol 934 ointments was significantly increased by adding Azone (AZ). Effective plasma levels were sustained for about 10-20 h, but the absorption of PL from the macrogol ointment was relatively slow. The bioavailability of PL in the 5% PL Carbopol ointment with AZ was 13%. The plasma level of PL after application of Carbopol ointment was enhanced as PL was increased in the ointment, 3 to 5%. The repeated p.c. absorption studies were carried out by applying the 5% PL ointment daily for 3 d. The use of the pharmacokinetic model was justified by good agreement with the observed data after repeated applications of the ointment. Thus, the plasma PL concentration profile during repeated p.c. administrations can be predicted using the model.