【摘要】 目的观察随年龄增长所致的肾功能减退对头孢哌酮(CFZ,第3代头孢类抗生素)/舒巴坦(SBT,β内酰胺酶抑制剂)药代动力学的影响。方法44名健康成年与老年受试者,每12h静脉给予CFZ/SBT各1g,共7次,采集末次给药后不同时间的血样,用HPLC方法测定血药浓度;肌酐清除率(Ccr)用Cockcroftand Gault法计算。结果老年男性和成年男性Ccr分别为(65.3±7.7),(106.0±21.6)mL·min-1(P<0.01);稳态时,CFZ:AUC分别为(256.3±72.0),(182.3±49.6)mg·h·L-1(P<0.01);Cmax分别为(102.0±15.3),(89.4±10.7)μg·mL-1(P<0.05);t1/2分别为(2.2±0.6),(1.5±0.5)h(P<0.01);CLT分别为(4.2±1.2),(5.8±1.2)L·h-1(P<0.01),Ccr与CLT、AUC、t1/2相关(γ分别为0.52、-0.40、-0.27,均P<0.01)。稳态时,SBT:AUC分别为(81.8±28.4),(33.7±6.7)mg·h·L-1(P<0.01);Cmax分别为(54.7±19.9),(28.0±4.8)μg·mL-1(P<0.01);t1/2分别为(1.4±0.4),(1.1±0.5)h(P>0.05);CLT分别为(13.7±4.9),(30.6±5.2)L·h-1(P<0.01),Ccr与CLT、AUC、t1/2相关(γ分别为0.52、-0.44、-0.47,均P<0.01)。两药的CLT比值:SBT/CFZ分别为(3.43±1.42),(5.52±1.52)(P<0.01)。说明老年人对CFZ/SBT清除下降,以SBT为显著。结论老年的肾功能轻度减退,可造成CFZ/SBT药代动力学改变,SBT更明显。更多还原

【Abstract】 Objective To study the effect of aging kidney on pharmacokinetics of cefoperazone and sulbactam (1∶1). Methods Fourty-four healthy volunteers (adults: 12 male and 12 female;old: 20 male). Seven dose of 1 g cefoperazone (CFZ) and 1 g sulbactam (SBT) were administered intravenously q12 h. Concentrations of CFZ and SBT in samples collected at different time intervals after the last dosage were determined by HPLC. Ccr were calculated by Cockcroft and Gault formula.Results In aging male and adult male group: Ccr were (65.3±7.7),(106.0±21.6)mL·min-1 respectively(P<0.01). CFZ at steady state:AUC were(256.3±72.0),(182.3±49.6) mg·h·L-1 respectively( P<0.01);Cmax were(102.0±15.3),(89.4±10.7)μg·mL-1 respectively(P<0.05); t1/2 were(2.2±0.6),(1.5±0.5) h respectively (P<0.01); CLT were (4.2±1.2), (5.8±1.2) L·h-1 respectively (P<0.01). CLT,AUC,t1/2 were correlated with Ccr(γ=0.52,-0.40,-0.27 respectively,all P<0.01). SBT at steady state:AUC were (81.8±28.4),(33.7±6.7) mg·h·L-1 respectively( P<0.01);Cmax were (54.7±19.9),(28.0±4.8)μg·mL-1 respectively(P<0.01);t1/2 were (1.4±0.4),(1.1±0.5)h respectively (P>0.05),CLT were (13.7±4.9),(30.6±5.2)L·h-1 respectively(P<0.01). CLT, AUC, t1/2 were correlated with Ccr(γ=0.52, -0.44, -0.47 respectively,all P<0.01).CLT of SBT/ CLT of CFZ in aging male group and adult male group were (3.43±1.42), (5.52±1.52), respectively(P<0.01). It was illustrated that the clearance rate of CFZ/SBT reduced in aging male by predominate SBT.Conclusion Reduced renal function result from aging can cause pharmacokinetic changes of CFZ/SBT.更多还原