Pharmacokinetics And Relative Bioavailability Of Tebipenem Pivoxil Tablets In Beagle Dogs

Objective:With than from the south to the production for horse ester piece for the test preparation,Japan Meiji company production for than Mr South horse ester particles（trade name:オラペネム?small where with fine grained 10%）as the reference preparations,comparison in Beagle dogs in vivo pharmacokinetic parameters and relative bioavailability,than from the south for horse ester preparation bioequivalence evaluation to provide the reference.Methods:The experiments were divided into fasting administration test and eating administration test,all of which adopted self-designed double-cross experiment design,and the washing per iod between the two weeks was one week.Eight healthy Beagle dogs,half male and half fem ale,were selected and divided into two groups with 4 dogs in each group.The reference prep aration was prepared with 0.5%sodium carboxymethyl cellulose before administration,maki ng the dosage of both preparations 125mg/dog.The fasting group was free to drink water an d fasting for about 12h before administration,and unified feeding for 2h after administration.2m Lblood was collected from the saphenous VVvein of the forelimb at 0h before administra tion and 0.17,0.33,0.67,1.0,1.5,2.0,3.0,5.0 and 7.0h after administration.The feeding grou p fasted for 12h and abstained from water 1h before administration,.Each dog was uniform L y fed 150g of feed and 100m L of water 30 minutes before administration.2m Lblood was co llected from the saphenous vein of the forelimb before（0h）and 0.25,0.5,1.0,1.5,2.0,3.0,4.0,5.0,6.0 and 7.0h after administration,respectively.The concentration of tibipenem in plas ma was determined by HCLP-MS/MS method.DAS2.0 was used to process the data,AUC and T_1/2were calculated by statistical moment method,and Tmax and Cmax were measured.According to AUC_0^tof the test preparation and reference preparation,the relative bioavaila bility F_0^t%of the test preparation relative to the reference preparation was calculated by the following formula.F_0^t%=AUC_0^tof test preparation/AUC_0^tof reference preparation×100%.Results:The method was proved to be specific and there were no interfering substances in blank plasma.The regression equation of standard curve was Y=0.0018x-0.00493,r=0.9956,the l inear range was 26.00ng/m L～6320ng/m L,the lower limit of quantification was 26.00ng/m L,the precision and accuracy were good,the extraction recovery was high,there was no obvio us matrix effect,and the stability was good.Meet the requirements of biological sample analy sis.After oral administration of the test preparation and reference preparation,the main phar macokinetic parameters of Beagle dogs were（0.59±0.14）and（0.66±0.17）h for T_1/2under f asting condition.T_maxwas（1.29±0.38）and（0.94±0.28）h;C_maxwere（4269±1847）and（3031±1115）ng/m L;AUC_0-twere（6893±2942）and（4628±1780）ng/m L·h;AUC_0-∞were（6939±2948）and（4653±1777）ng/m L·h.The relative bioavailability of the two was 149%.T_1/2was（0.65±0.15）and（0.56±0.12）h under feeding condition;T_maxwas（1.44±0.68）and（1.19±0.37）h;C_maxwere（3834±1321）and（2009±1179）ng/m L;AUC_0-twere（5655±1351）a nd（2881±1484）ng/m L·h;AUC_0-∞is（5757±1370）and（2940±1473）ng/m L·h.The relat ive bioavailability of the two was 196%.Conclusion:The HPLC-MS/MS method established in this study is simple,reliable,accurate and sensitive for the detection of the blood concentration of tibipenem in Beagle dog plasma,which is suitable for the pharmacokinetic study of tibipenem.The relative bioavailability of tibipenempithyl granules and tibipenempithyl tablets was not consistent.