西咪替丁对大鼠体内呋喃氟脲嘧啶药代动力学的影响

本文用交叉实验设计法研究了西咪替丁(Cim)对9只大鼠口服呋喃氟脲嘧啶(FT—207)药代动力学的影响。反相HPLC法测定血清FT-207浓度,其药时曲线符合一室开放模型。单次口服Cim80mg/kg或连用Cim80 mg/kg·d~(-1)×5d,均增加血清FT—207浓度和AUC。连用时,FT-207的C_(max)和AUC分别增加21.0%(P<0.05)和34.1%(P<0.025),Te_(1/2)缩短(P<0.005);单次服Cim时,FT-207的药代学改变与连用时相似,但差异无显著性。文中讨论了二药相互作用的机制及临床意义。

THE INFLUENCE OF CIMETIDINE ON THE PHARMACOKINETICS OF FTORAFUR IN RATS

The influence of cimetidine on the pharmacokinetics of ftorafur ( FT-207 ) in 9 rats after intragastric administration were investigated with cross-over design. The concentration of ftorafur in serum was determined by reversed-phase HPLC. Its curve of concentration vs time was fit to one compartment opened model. The serum concentrations and areas under the curve ( AUC ) vs time were increased when cimetidine orally administered daily for 5d or single dose. The peak of serum and AUC of ftorafur were increased by 21 .0%(P<0.05) and 34.1% ( P<0.025 ) respectively. Its Te1/2 was decreased ( P<0 .005 ) after intragastric administration of cimetidine 80mg/kg · d-1 for 5d.The similar pharmacokinetic changes of ftorafur were obtained after single dose of cimetidine, but there was no significant difference.The mechanism of interaction between cimetidine and ftorafur and its clinical significance were discussed in this paper.