中国临床药学杂志

目的研究复方磺胺甲(口恶)唑(SMZco)对环孢素A(CsA)在兔体内药动学特征的影响。方法 6只(?)性日本大耳白兔,采用自身对照法,予CsA 9 mg·kg^-1,ig,bid,连续灌胃给药7 d,于第8天应用LC-MS方法测定兔体内CsA浓度,DAS软件分析其药动学特征。完成CsA浓度检测后,即联用SMZco,37 mg·kg^-1,ig,bid,1周后再次测定CsA的药动学特征,获得主要药动学参数,统计分析。结果联用SMZco前后CsA在兔体内的主要药动学参数分别是AUC_0→∞(9 262.764±3 060.376)、(5 729.079±343.687)μg·h·L^-1;MRT_0→∞(14.669±6.487)、(5.973±1.409)h;t_1/2(8.791±4.321)、(3.14±1.356)h;ρ_max(784.4±392.59)、(1 066.833±279.593)μg·L^-1。联用SMZco后CsA的AUC_0→∞,MRT和t_1/2均缩短,且差异均有统计学意义(P<0.05)。结论 SMZco与CsA联合给药时,可促进CsA的体内代谢,缩短体内滞留时间。

AIM To study the effect of compound sulfamethoxazole(SMZco) on pharmacokinetics of cyclosporin A(CsA)in rabbits.METHODS Six rabbits were randomly involved in a self-controlled study,and 9 mg·kg^-1 CsA was administrated intragastrically twice a day for a week.The concentrations of CsA were determined by LC-MS method at 8d and the pharmacokinetic parameters were analyzed by DAS software.Subsequendy,SMZco 37 mg·kg^-1 combined with CsA were administrated intragastrically twice a day for a week,then the phannacokinetic parameters of CsA in rabbits were determined using the same method as above.All data were analyzed by statistical method.RESULTS The pharmacokinetic parameters of CsA before and after administration with SMZco were AUC_0→∞(9 262.764±3 060.376),(5 729.079±343.687)μg·h·L^-1;MRT_0→∞(14.669±6.487),(5.973±1.409)h;t_1/2(8.791±4.321),(3.14±1.356)h;ρ_max(784.4±392.59),(1066.833±279.593)μg·L^-1,respectively.The AUC,MRT and t_1/1 of CsA all increased after administration with SMZco(P < 0.05).CONCLUSION The metabolism of CsA will be promoted and the residence time will be decreased in rabbits when combined with SMZco.