Effect of clarithromycin on the pharmacokinetics of glipizide in rabbits

AIM To study the influence of clarithromycin on the pharmacokinetics of glipizide in healthy and dia- betic rabbits.METHODS Glipizide(5 mg) was taken orally once to every rabbit.After 2 weeks of clearing stage,clarithromycin (0.25 g) was administered daily by intraperitoneal injection bid for 3 d,then glipizide was taken orally at the same dosage on the fourth day.The blood was drawn from ear vein 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 HPLG.The pharmacokinetic parameter was calculated by 3P97 software.The pharmacokinetics of glipizide in rabbits administered with or without clarithromycin 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_(1/2ke).ρ_(max) and AUC values were(3.99±1.52)h, (4.05±0.89)mg·L~(-1) and(68.54±15.67)mg·h·L~(-1),respectively.In healthy rabbits administered with glipizide and clarithromycin,the t_(1/2)ke,ρ_(max) and AUC values were(4.26±1.29)h,(5.41±1.64)mg·L~(-1) and(74.25±18.94) mg·h·L~(-1),respectively.In diabetic rabbits administered with glipizide,the t_(1/2ke),ρ_(max) and AUC values were(3.81±0.89)h,(4.19±1.25)mg·L~(-1),(70.24±13.21)mg·h·L~(-1),respectively.In diabetic rabbits administered with glipizide and clarithromycin,the t_(1/2ke),ρ_(max) and AUC values were(4.28±0.91)h,(5.31±1.47)mg·L~(-1) and(79.48±17.69)mg·h·L~(-1) respectively.There were notable differences on t_(1/2ke),ρ_(max) AUC values of glipizide in rabbits administered with or without clarithromycin.CONCLUSION Clarithromycin shows significant inhibition on the pharmacokinetics of glipizide.