Study Of The Serum Bactericidal Activity And Pharmacokinetics Of Gatifloxacin

OBJECTIVE To evaluate antibacterial activity in vitro of gatifloxacin and levofloxacin ,and study serum bactericidal titer of gatifloxacin; build the HPLC- fluorescence method about the concentration of gatifloxacin in serum, and research on its pharmacokinetics in vivo.Method Minimal inhibitory concentration(MIC) and serum bactericidal titerwere determined by agar disk dilution method and microplate method, and use levofloxacin as control. Vein drip(VD) 400mg gatifloxacin to 8 health persons,.and take the immediate and 24 hours later blood to test the SET. Based on the latin square Randomly group ,the 9 persons who take part in the single administration experiment. To alternate drip three doses gatifloxacin as 100mg, 200mg, 400mg, to use the HPLC-fluorescence method to test its blood concentration at different time points.Basing on the standard curve, calculate its corresponding concentration, and calculate its pharmacokinetics parameters.Result As to the vitro antibacterial activity against G+ bacteria, gatifloxacin is better than levofloxacin. MICgo of gatifloxacin against G+ bacteria was 2 ~ 4 times lower thanlevofloxacin. As to the vitro antibacterial activity to G" bacteria, its effect was similar to levofloxacin. Its SET 1 : 8 to staphylococcus aureus staphylococcus epidermidis , K.pneumoniae , E.cloacae are 100%, 90% > 100%, 100% respectively. The percent age of peak SBT^l ! 8 to E.faecalis> coli bacillus > pseudomonas aeruginosa was 50%> 60% > 50% respectively. After volunteers were alternately vein dripedgatifloxacin lOOmg , 200mg , 400mg , the plasma concentration-time curves was fitted to two-compartment open model. The major pharmacokinetics parameters: Cmax are 1.098 + 0.190 ug.ml-1, 2.170?.329 u g.ml-1, 3.164 + 0.473 u g.mr-1; t1/2 was 7.415 + 1.958h, 8.413?.722h, 8.462?.832h; AUCV-was 4.45?.712mg.L"1.h, 11.102+1.841 mg.L"'.h, 23.029 +3.835 mg-U-1h; Tmax was 0.50+Oh, 1.0+0.0h, 2.0+0.01h.CONCLUTION The antibacterial activity in vivo and in vitro of gtifloxacin against common bacterium were strong, even the antibacterial activity in vitro of gatifloxacin is stronger than levofloxacin. After volunteers were alternately vein dripedgatifloxacin lOOmg , 200mg , 400mg , the plasma concentration-time curves was fitted to two-compartment open model.The pharmacokinetics parameters t1/2 ,Kel,CL has no relation to the dose,Tmax is related to administration time, AUCo~ became bigger when we increased the dose.No adverse reaction was found in volunteers during the experiment.