Effects of Biapenem on the Distribution of Valproic Acid in Inner and Outer Sides of Erythrocyte of Rats

OBJECTIVE:To investigate the effect of biapenem on the distribution of valproic acid(VPA)in inner and outer sides of erythrocytes of rats.METHODS:Rats were randomly assigned into control group(VPA 50 mg·kg-1)and trial group(biapenem 15 mg·kg-1+VPA 50 mg·kg-1)with 6 rats in each group.Rats were fasting 12 hours.After the rats were anesthetized,cannulation(closed catheter system)was made at femoral vein and artery.Heparin was injected before giving medicine via femoral vein.The blood and plasma VPA levels were determined by fluorescence polarization immunoassay(FPIA)180 min after administration.Pharmacokinetic parameters were calculated using non-compartment model.RESULTS:Compared with control group,the VPA level in blood sample of trial group had no obvious change while VPA level in plasma sample decreased.Then we estimated that VPA level in erythrocytes increased.The pharmacokinetic parameters of VPA in trial group vs.control group were as follows:AUC0-3 h:(134.89±18.88)μg·h·mL-1 vs.(189.35±34.76)μg·h·mL-1;t1/2:(0.95±0.04)h vs.(1.13±0.16)h.The results showed that the AUC0-3 h and t1/2 had significant difference between 2 groups(P0.05).CONCLUSION:Biapenem increases the distribution of VPA in erythrocytes,while it markedly reduces VPA levels in plasma.