Comparative bioavailability of L-683,453, a 5α-reductase inhibitor, from a self-emulsifying drug delivery system in Beagle dogs

摘要: Bioavailabilities (BA) of the lipophilic compound, L-683,453, from several formulations were determined in fasted and fed purpose-bred Beagle dogs following oral administration an i.v. reference dose. The compound is poorly soluble water (∼0.001 mg/mL) exhibited very low BA, 0.2%, suspensions methyl cellulose, dogs. Addition sodium dodecyl sulfate (SDS) into increased BA significantly to 0.6% (P = 0.05) 1.7% animals < 0.01). A more dramatic enhancement up 13.7%, was achieved a self-emulsifying formulation composed mono- di-glycerides caprylic/capric acids (MDG) surfactants. It found that tolerability efficacy MDG-based at 16 mg/kg depend not only on dose but also dosing volume. volume 2 mL/kg caused emesis, while 1 well tolerated. In contrast its effect suspensions, food had no statistically significant volumes 0.25 mL/kg. However, peak plasma concentrations faster than animals.