Pharmacokinetics of propafenone hydrochloride sustained-release capsules in male beagle dogs.

This paper describes the development and validation of a liquid chromatography–mass spectrometric assay for propafenone and its application to a pharmacokinetic study of propafenone administered as a new propafenone hydrochloride sustained-release capsule (SR-test), as an instant-release tablet (IR-reference) and as the market leader sustained-release capsule (Rythmol, SR-reference) in male beagle dogs (n=8). In Study A comparing SR-test with IR-reference in a crossover design Tmax and t1/2 of propafenone for SR-test were significantly higher than those for IR-reference while Cmax and AUC were lower demonstrating the sustained release properties of the new formulation. In Study B comparing SR-test with SR-reference the observed Cmax and AUC of propafenone for SR-test (124.5±140.0ng/mL and 612.0±699.2ng·h/mL, respectively) were higher than for SR-reference (78.52±72.92ng/mL and 423.6±431.6ng·h/mL, respectively) although the differences were not significant. Overall, the new formulation has as good if not better sustained release characteristics to the market leader formulation.