Abstract: AIM: To study the influence of roxithromycin on the pharmacokinetics of glipizide capsule in healthy and diabetic rabbits METHODS: Glipizide (5 mg) was taken orally once to every rabbit. After 2 weeks of clearing stage, roxithromycin (50.0 mg) was administered daily by intra peritoneal injection bid for 3 d,then glipizide was taken orally at the same dosage on the 4 d. The blood was drawn from ear vein before and at 0.5, 1.5, 3, 5, 7, 9, 11,24 and 35 h after administering glipizide in every rabbit. Then the blood concentration of glipizide was measured by HPLC. The pharmacokinetic parameter was calculated with pharmacokinetic software DAS2.0. The pharmacokinetics of glipizide in rabbits administered with or without roxithromycin were analyzed by auto-control.RESULTS: The concentration time-curves were fit to the one-compartment model. In healthy rabbits administered with glipizide, the t_1/2, C_max, AUC values were (2.9±0.4) h , (5815±940) μg/L, (58919±860)μg·h·L^-1. In healthy rabbits administered with glipizide and roxithromycin, the t_1/2, C_max, AUC values were (3.5±0.9) h, (6165±764)μg/L , (76515±1830) μg·h·L^-1.In diabetes rabbits administered with glipizide, the t1/2, C_max, AUC values were (1.7±0.4) h, (4307±580) μg/L, (32469±786)μg·h·L^-1. In diabetes rabbits administered with glipizide and roxithromycin, the t_1/2, C_max, AUC values were (3.2±1.5)h,(8531±1479) μg/L,(76489±1588) μg·h·L^-1. There were notable differences on t_1/2, C_max, AUC values of glipizide in rabbits administered with or without roxithromycin.CONCLUSION: Roxithromycin shows significant inhibition on the pharmacokinetics of glipizide. The two drugs in clinical share requiring attention adjustment dose in order to avoid hypoglycemia hazards.

Key words: Glipizide, Roxithromycin, Interaction, Diabetes mellitas rabbit