ABSTRACT
Objective To investigate effects of diabetes mellitus (DM) on pharmacokinetics (PK) of cephradine (CED).Methods DM model was induced by iv.alloxan 60 mg·kg-1.A reversed phase HPLC internal standard method was developed for measurement of CED plasma concentration.After blood collection,rats were sacrificed to collect kidneys for calculating kidney index(KW/BW).DM and normal control (CTL) rats were randomly assigned to receive iv.or ig.CED at a dose of 180 or 90 mg·kg-1.The 3p97 program was used to calculate PK parameters.Results The developed HPLC method was validated to have high specificity,precision,recovery and good storage stability,and met requirements for PK study of CED.The CED in rats of both DM and CTL groups showed the iv.two-compartment PK and ig.one-compartment PK and followed the first-order kinetics.Following iv.dosing,a remarkably decreased t1/2β and MRT,increased CLt were evident in DM group as compared with CTL group (P ＜ 0.05).After ig dosing,a significant decrease in t1/2k and t a remarkable increase in CLt and Cm=were observed for DM group as compared with CTL group (P ＜ 0.05).The DM rats showed a trend of decreased t1/2ka vs CTL rats.There was no significant difference in the oral bioavailability between the two groups (P ＞ 0.05).KW and KW/BW in DM group were increased remarkably compared with CTL group (P ＜ 0.05).Conclusion The DM vs CTL results in faster absorption and elimination of CED in rats,but does not have significantly affect in oral bioavailability.The compensatory hypertrophy and hyperfunction of early-stage diabetic kidneys may constitute one of causes of quick elimination of CED in rats with DM.
ABSTRACT
Aims & Methods: The present study was undertaken to compare the antibacterial activity of a cephradine derivative with that of the parent antibiotic cephradine. Cephradine was converted to its benzoyl derivative by Schotten-Baumann method for the first time. Disc diffusion method was employed to find out the antibacterial activity against EPEC, ETEC, E. Agg, Salmonella typhi, Salmonella group B, Shigella boydii, Shigella dysenteriae 1, Shigella dysenteriae 2, Shigella flexinariae and Shigella sonnei. Melting point, TLC, HPLC, UV, FTIR and 1H NMR studies were carried out to check the purity and confirm that the derivative was cephradine benzoate. Results: The benzoyl derivative showed promising activity against tested bacteria. The results obtained from the study demonstrate that the benzoyl derivative could be a potential antibacterial agent.