Objective To study effects of diabetes mellitus(DM)on pharmacokinetics of cephradine(CED)by comparing the difference in pharmacokinetic behaviours of CED between diabetic and normal rats.Methods DM was induced in male rats by a single iv injection of alloxan 60 mg·kg-1;rats whose blood glucose was over 16 mmol·L-1 were taken as DM group.The rats were divided into DM group and normal control(CTL)group,which were subdivided into low dose(90 mg·kg-1)and high dose(180 mg·kg-1)subgroups.CED was administered by iv or po routes.Blood samples collected at different time post dosing were analyzed by RP-HPLC to yield CED plasma concentration time course.Chromatographic separation was achieved on a Kromasil C18 column(250×4.6 mm ID,5 μm);mobile phase,consisting of 0.025 mol·L-1 KH2PO4-MeOH-CH3CN(87;6∶7 v/v),was delivered at 1.0 mL·min-1;UV detector was set at 261 nm.The peak area ratio of CED to cephalexin(CEX)as internal standard vs concentraion of CED was used to construct calibration curve.50 μL aliquots of TCA-deproteined plasma samples were injected into chromatograph.Results The methodology validation including specificity,precision,accuracy,recovery,limit of quantitation,linearity,stability,etc.,showed that the HPLC assay developed by us completely met requirements of pharmacokinetic study Both DM and CTL groups showed the two-compartment model for iv dosing and extravascular one-compartment model for po dosing as well as first-order kinetics.However,in iv experiment,DM group,when compared with CTL group,presented a significantly shortened t1/2β and MRT as well as increased CL,reflected by t1/2 β 84-91 vs 116-120 min,MRT 61-70 vs 103-119 min;CL 23-25 vs 18-19 mL·min-1·kg-1(P<0.05);in po experiment,a markedly shorter t1/2 K and tmax as well as greater CL and Cmax in DM group than in CTL group were found;meanwhile,DM rats suffered from remarkably increased kidney weight(KW)and KW/BW ratio relative to CTL rats.Conclusions DM pathological status can speed up elimination of CED from body of rats;the compensatory hypertrophy and thereby hyperfunction of kidneys in early-stage diabetics may explain in part at least this accelerated elimanation. Objective To study effects of diabetes mellitus (DM) on comparingokinetics of cephradine (CED) by comparing the difference in pharmacokinetic behaviors of CED between diabetic and normal rats. Methods DM was induced in male rats by a single iv injection of alloxan 60 mg · kg -1; rats whose blood glucose was over 16 mmol·L-1 were taken as DM group. These rats were divided into DM group and normal control (CTL) group, which were subdivided into low dose (90 mg · kg -1) and high dose (180 mg · kg -1) subgroups. CED was administered by iv or po routes .lood samples collected at different time post dosing were analyzed by RP-HPLC to yield CED plasma concentration time course. Chromatographic separation was achieved on a The mobile phase, consisting of 0.025 mol·L-1 KH2PO4-MeOH-CH3CN (87; 6: 7 v / v) was delivered at 1.0 mL · min -1 (250 × 4.6 mm ID, ; UV detector was set at 261 nm. The peak area ratio of CED to cephalexin (CEX) as internal standard vs concentraion of CED was used to construct calibration curve.50 μL aliquots of TCA-deproteined plasma samples were injected into the chromatograph. Results The Method validation including specificity, precision, accuracy, recovery, limit of quantitation, linearity, stability, etc., showed that the HPLC assay developed by us completely met requirements of pharmacokinetic study Both DM and CTL groups showed the two-compartment model for iv dosing and extravascular one-compartment model for po dosing as well as first-order kinetics. Still, in iv experiment, DM group, when compared with CTL group, presented a marked shortened t1 / 2β and MRT as well as increased CL, reflected by t1 / 2 β 84-91 vs 116-120 min, MRT 61-70 vs 103-119 min; CL 23-25 ​​vs 18-19 mL · min-1 · kg-1 (P <0.05); in po experiment, a markedly shorter t1 / 2 K and tmax as well as greater CL and Cmax in DM group than in CTL group were found; increased kidney weight (KW) and KW / BW ratio relative to CTL rats. Conclusions DM pathological status can speed up Elimination ofCED from body of rats; the compensatory hypertrophy and thereby hyperfunction of kidneys in early-stage diabetics may explain in part at least this accelerated elimanation.