The Preliminary Study Of Pharmacokinetic Changes And Drug Interaction Under Different Pathological Conditions

AIM1To evaluate the pharmacokinetics of carbamazepine, rifampicin and metformin hydrochloride in mice with cholecystectomy.2To study the pharmacokinetics of breviscapine and the effect of Huangqi injection on the pharmacokinetics of breviscapine in normal and diabetic rats.3To compare the pharmacokinetic differences of gliquidone in normal and diabetic rats, and study the effect of breviscapine or Huangqi injection on the pharmacokinetics of gliquidone in normal and diabetic rats, respectively.METHODS1The mice were raised under normal conditions for two weeks after operation. The mice were administered orally with carbamazepine, rifampicin or metformin hydrochloride, respectively, and the blood samples were collected at different time. The concentration of carbamazepine, rifampicin or metformin hydrochloride in plasma were determined by HPLC, and the pharmacokinetics parameters were calculated with the software of DAS2.0.210normal rats were randomly divided into Group A and B, and ten diabetic model rats induced by streptozotocin were randomly divided into Group C and D.(1) Rats in Group A and C were administered intravenously with breviscapine aqueous solution at a single dose of16mg/kg.(2) Rats in Group B and D were administered intravenously with breviscapine aqueous solution (16mg/kg) after being intravenously administered with Hangqi injection for5min. The blood samples were collected at different time, and the concentration of breviscapine in plasma were determined by HPLC, and the pharmacokinetic parameters of breviscapine were calculated with the software of DAS2.0.315normal rats were randomly divided into Group A, B and C, and15diabetic model rats induced by streptozotocin were randomly divided into Group D, E and F.(1) Rats in Group A and D were administered orally with gliquidone solution at a single dose of120mg/kg.(2) Rats in Group B and E were administered orally with gliquidone solution (120mg/kg) after being intravenously administered with breviscapine16mg/kg for5min.(3) Rats in Group C and F were administered orally with gliquidone solution (120mg/kg) after intravenous administration with Huangqi injection8ml/kg for5min. The blood samples were collected at different time, and the concentration of gliquidone in plasma were determined by HPLC-fluorescence. According to the curve of concentration-time, the software of DAS2.0was used to process the pharmacokinetic parameters.RESULTS1The main pharmacokinetic parameters of carbamazepine have no significant differences between sham-operated and operated group. The Tmax, t1/2, AUC and CL of rifampicin between sham-operated and the operated groups have significant differences(P<0.01); The Tmax and CL of metformin hydrochloride between the sham-operated and the operated groups have differences (P<0.05), the AUC of metformin hydrochloride was decreased, but without siginificant difference.2(1) The t1/2α, Cmax, AUC and CL in diabetic groups have siginificant differences compared with normal groups.(2) The AUC and Cmax of breviscapine were significantly increased and the CL was decreased when co-administering with Huangqi injection (P<0.01).3(1) The main pharmacokinetic parameters of gliquidone have siginificant differences between the normal and diabetic (P<0.01).(2) Breviscapine has no significant effect on the pharmacokinetics of gliquidone in normal or diabetic model rats, but the AUC of gliquidone was significantly increased and the CL was decreased when co-administering with Huangqi injection in normal and diabetic model rats (P<0.01).CONCLUSION1The pharmacokinetic parameters of lipophilic drug rifampicin have greatly changed in mice with cholecystectomy, but this effect is not as much as that on lipophilic drug carbamazepine and hydrophilic drug metformin hydrochloride.2(1) Pharmacokinetic parameters of breviscapine were significant differences between the normal and diabetic groups.(2) Huangqi injection has greatly effect on pharmacokinetics of breviscapine both in normal and diabetic model rats.3(2) The main pharmacokinetic parameters of gliquidone were siginificant differences between normal and diabetic model rats.(2) Breviscapine has no effect on pharmacokinetics of gliquidone.(3) Huangqi injection has significant effects on the pharmacokinetics of gliquidone both in normal and diabetic rats.