OBJECTIVE: The aim of this study was to determine the effect of DEX on plasma and lung pharmacokinetics of MFX in male and female rats.
METHODS: A total of 132 rats were randomly divided into 2 groups: MFX (n=66, 33 males/33 females) and MFX+DEX (n=66, 33 females/33 males). MFX at a dose of 20 mg/kg and DEX at a dose of 25 mg/kg were administered intraperitoneally. Plasma and lung concentrations of MFX were determined using the highperformance liquid chromatography-UV and pharmacokinetic parameters were evaluated by noncompartmental analysis.
RESULTS: Simultaneous administration of DEX increased the plasma and lung area under the curve from 0 to 8 h (AUC0-8) and peak concentration (Cmax) of MFX in rats, while it significantly decreased the total body clearance (CL/F). When female and male rats were compared, significant differences were detected in AUC0-8, Cmax, CL/F and volume of distribution. The AUC0-8lung/AUC0-8plasma ratios of MFX were calculated as 1.68 and 1.65 in female rats and 5.15 and 4.90 in male rats after single and combined use, respectively.
CONCLUSIONS: MFX was highly transferred to the lung tissue and this passage was remarkably higher in male rats. However, DEX administration increased the plasma concentration of MFX in both male and female rats but did not change its passage to the lung. However, there is a need for a more detailed investigation of the difference in the pharmacokinetics of MFX in male and female rats.
目的:本研究的目的是确定DEX对MFX在雄性和雌性大鼠中的血浆和肺药代动力学的影响。
方法:将132只大鼠随机分为2组:MFX组(n=66,雄性33只/雌性33只)和MFX+DEX组(n=66,雌性33只/雄性33只)。腹膜内施用20mg/kg剂量的MFX和25mg/kg剂量的DEX。使用高效液相色谱-UV测定MFX的血浆和肺浓度,并通过非房室分析评估药代动力学参数。
结果:同时服用DEX增加了大鼠血浆和肺在0至8h的曲线下面积(AUC0-8)和MFX的峰值浓度(Cmax),而显着降低了全身间隙(CL/F)。当雌性和雄性大鼠进行比较时,在AUC0-8、Cmax、CL/F和分配量。单独和联合使用后,MFX的AUC0-8肺/AUC0-8血浆比率在雌性大鼠中计算为1.68和1.65,在雄性大鼠中计算为5.15和4.90,分别。
结论:MFX高度转移到肺组织,并且在雄性大鼠中这种传代明显更高。然而,DEX给药增加了雄性和雌性大鼠中MFX的血浆浓度,但没有改变其向肺的通过。然而,需要更详细地研究MFX在雄性和雌性大鼠中的药代动力学差异。