PHARMACOKINETICS AND RELATIVE BIOAVAILABILITY OF PROBUCOL INCLUSION COMPLEX CAPSULE IN HEALTHY DOGS

AIMTo study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule. METHODSFollowing oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed. RESULTSThe concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The T_max values of formulation A and formulation B were (9.3±2.1) h and (9.3±2.1) h, the C_max values were (1.5±1.0) μg·mL^-1 and (2.3±0.9) μg·mL^-1 and the AUC_0～240 values were (85±56) μg·h·mL^-1 and (134±55) μg·h·mL^-1, respectively. The relative bioavailability of formulation B was found to be (198±90)% compared with formulation A. The results of variance analysis and two one-side t-test showed that there was significant difference between the two formulations in the AUC_0～240. CONCLUSIONThe high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.