PHARMACOKINETIC EVALUATION OF TRANSDERMAL BUPRENORPHINE IN MAN

Transdermal delivery of the synthetic opiate analgesic, buprenorphine, was studied in healthy volunteers. Pharmacokinetic, safety and tolera bility data were obtained in a group of 12 healthy subjects following administration of a short intravenous infusion and the application of both aqueous- and ethanol-based fillable transdermal therapeutic syste ms (FTTS), containing 8 and 37.5 mg of drug, respectively. The total a mount delivered by the 10 cm(2) aqueous reservoir system ranged from 0 .11 to 0.67 mg over the 24 h application period and the steady state i n vivo flux rates were 0.56-1.91 mu g/cm(2)/h. The total amount delive red by the 5 cm(2) ethanol-based FTTS ranged from 0.33 to 0.96 mg and the steady state in vivo flux values were 2.14-5.62 mu g/cm(2)/h. The results of the feasibility investigation demonstrated that transdermal delivery of buprenorphine produced sustained plasma levels of drug wi thin the range observed after intravenous dosing and that an ethanolic formulation produced approximately a four-fold increase in transderma l flux. The in vivo investigation suggests that transdermal delivery c ould provide appropriate plasma levels of buprenorphine for sustained analgesic effect.