膦甲酸钠对硫酸头孢噻利大鼠体内药动学的影响

Effect of Foscarnet Sodium on the Pharmacokinetics of Cefoselis Sulfate in Rats

考察了膦甲酸钠对硫酸头孢噻利在大鼠体内药动学的影响。健康Wistar大鼠随机分为试验组与对照组,每组20只。试验组大鼠尾静脉注射膦甲酸钠360 mg/kg,随后即刻注射硫酸头孢噻利200 mg/kg;对照组仅注射硫酸头孢噻利200 mg/kg。采用HPLC法测定血浆中硫酸头孢噻利浓度,并拟合药动学参数,试验组和对照组结果如下:t1/2(1.76±0.57)和(1.22±0.51)h,cmax(1 314.37±196.70)和(1 470.18±321.38)μg/ml,AUC0→24 h(863.19±189.46)和(799.57±203.39)μg·h·ml-1,AUC0→∞(898.81±214.25)和(800.02±207.04)μg·h·ml-1,V(0.56±0.18)和(0.45±0.17)L/kg,CL(0.23±0.05)和(0.27±0.07)L·h-1·kg-1。合用膦甲酸钠后,硫酸头孢噻利在大鼠体内的t1/2和V显著升高,表明膦甲酸钠与硫酸头孢噻利可能竞争同一排泄途径,减缓硫酸头孢噻利的排泄。

The influence of foscarnet sodium on the pharmacokinetics of cefoselis sulfate in rats was investigated. Rats were randomly divided into test group and control group with 20 rats in each. Foscarnet sodium （360 mg/kg） was given to the test group by intravenous injection via vena caudalis, and then cefoselis sulfate （200 mg/kg） was given immediately by the same route. While the control group was given cefoselis sulfate （200 mg/kg） intravenously. An HPLC method was applied for the determination of cefoselis sulfate concentration in plasma. The pharmacokinetic parameters of the test and the control group for cefoselis sulfate were calculated as follows： tl/z （1.76±0.57） and （1.22±0.51）h, Cmax （1 314.37±196.70） and （1 470.18±321.38）μg/ml, AUC0→24h （863.19±189.46） and （799.57± 203.39）μg·h·m1-1, AUC0→∞ （898.81±214.25） and （800.02±207.04）μg·h·ml -1, V （0.56±0.18） and （0.45±0.17）L/kg, CL （0.23±0.05） and （0.27±0.07）L·h·kg-1, respectively. The results showed that the values of t1/2 and V increased significantly when co-administered with foscamet sodium in rats, which indicated that foscamet sodium might inhibit the excretion of cefoselis sulfate by competing the excretion pathway in kidney.