The Pharmacokinetics Study On The Impacts Of Probenecid To Ampicillin In Dogs

Aim: To develop a LC/MS/MS method for determination of ampicillin and probenecid in beegles dogs' plasma. Use this method, we could obtain the concentration-time profiles of the two drugs. Furthermore, after calculated the PK parameters, the main parameters obtained were analyzed by ANOVA.Method: To study the different behaviors on pharmacokinetics of ampicillin (reference) and ampicillin / probenecid (test) after administrated to 6 beegles dogs designed by two period cross-over at high, middle and low dose level, respectively. The concentration was determined by LC/MS/MS and a concentration-time profiles could be obtained. The values of AUC were calculated with trapezoid method, t1/2 was calculated according to the last four points in the elimination phase. Results and conclusion: The values of t1/2 of ampicillin (in the reference group) in 6 beegles dogs are 0.70±0.10, 0.92±0.07 and 1.49±0.13 h at the intravenous dosage of 40, 80 and 160 mg(kg-1 respectively. And the values of AUC0-t were 129.8±28.04,142.8±24.92 and 233.7±48.71 (g(h(ml-1, the values of AUC0-( were 130.1±28.07,143.0±24.94 and 234.0±48.78 (g(h(ml-1, respectively. However, the corresponding values of ampicillin (in the test group) were as follows: t1/2, 0.98±0.09, 1.15±0.11and 1.75±0.21 h; AUC0-t, 160.2±16.27, 171.8±41.79 and 275.5±79.55 (g(h(ml-1; AUC0-(, 160.5±16.29, 172.1±41.79 and 276.1±79.77 (g(h(ml-1。The values of t1/2 of probenecid in the test group were 10.63±3.92 , 13.78±5.06 and 9.91±2.93 h; The values of AUC0-t were 709.4±170.5, 1832.6±650.8 and 2632.8±980.2 (g(h(ml-1; And the values of AUC0-( were 756.3±216.2, 2250.6±994.9 and 2773.2±1101.9 (g(h(ml-1, respectively. The main parameters including t1/2 ,AUC0-t and AUC0-( were analyzed with ANOVA(AUC0-t and AUC0-( were transferred by logarithm first). The results showed that there were significant differences in these three parameters in the two groups. Contrary to the reference group, the values of t1/2 were longer and the values of AUC0-t and AUC0-( were higher in the test group. All of these indicated that probenecid could reduce the elimination rate of ampicillin in beegles dog after intravenously dosed.