高效液相色谱法测定羟甲烟胺对环孢菌素A药物动力学参数的影响

Influence of nicotinylmethylamide on the pharmacokinetic parameters of cyclosporin A by HPLC

目的 :建立简单、快速、准确的高效液相色谱法 (HPLC)测定环孢菌素A(cyclosporinA ,CsA)血药浓度的方法 ,研究羟甲烟胺对CsA药物动力学参数的影响。方法 :采用HPLC法测定 18名健康志愿者单服CsA及同服羟甲烟胺后CsA的血药浓度 ,用3p97分析处理数据 ,比较两组药动学参数的变化。结果 :单服CsA及同服羟甲烟胺后CsA的Cmax和AUC0～∞ 有极显著性差异 (P <0 .0 1) ,而t1/2 ( β) 、Tmax无显著性差异 (P >0 .0 5 )。结论 :本实验建立的HPLC法准确可靠 ,操作简便 ,适用于临床药动学研究及常规血药浓度监测。羟甲烟胺可促进CsA的吸收 ,提高CsA的峰浓度及药时曲线下面积 ,但不影响CsA的代谢。

AIM: To establish a simple, rapid and accurate high performance liquid chromatographic method (HPLC) for the determination of cyclosporin A (CsA) in human whole blood, and to study the influence of nicotinylmethylamide (Nic) on the pharmacokinetic parameters of cyclosporin A (CsA). METHODS: Whole blood CsA concentrations were measured by HPLC in 18 healthy volunteers administrated single CsA or co administrated Nic. The data of time blood concentrations of CsA were analyzed by 3p97 Program. The analysis of variance and two one sided t test were used to compare the main pharmacokinetic parameters of CsA in the two administrations. RESULTS: C max and AUC 0～∞ of CsA had statistically significance between the single CsA group and co administration of Nic group (P<0.01), while t 1/2(β) and T max of CsA had no statistically significance between the two groups (P>0.05). CONCLUSION: This HPLC method is simple, sensitive and accurate, and is suitable for routine determination of blood CsA levels in human. Nic can improve the absorption of CsA and increase the C max and AUC of CsA, but has no influence on the metabolism of CsA.