空腹与餐后条件下非洛地平缓释片在健康人体内的药代动力学比较研究

Comparison of pharmacokinetics of Felodipine Sustained-release Tablets in healthy volunteers under fasting and diet conditions

目的研究进食对口服非洛地平药代动力学参数的影响。方法使用液相色谱串联质谱(LC-MS/MS)法测定空腹及餐后条件下口服非洛地平缓释片后受试者血浆中药物浓度;计算两种条件下药动学参数与累计吸收百分数。结果采用非房室模型计算药动学参数,空腹组和餐后组的最大血药浓度(Cmax)分别为(1.57±0.83)、(5±2.36)ng·mL^-1;0~60h的血药浓度时间曲线下面积(AUC0~60)为(19.56±10.18)、(31.49±9.91)h·ng·mL^-1;0~∞时的血药浓度时间曲线下面积(AUC0~∞)分别为(21.98±11.53)、(34.1±10.97)h·ng·mL^-1;消除半衰期(t1/2)分别为(19.52±7.3)、(22.08±6.74)h;达峰时间(Tmax)分别为(4.12±2.26)、(4.17±1.13)h;清除率(Cl)分别为(290.53±149.81)、(161.33±51.7)L·h^-1;表观分布容积(Vz)分别为(7453.92±2994.86)、(5006.18±1828.22)L;最大血药浓度、0~60h的血药浓度时间曲线下面积、0~∞时的血药浓度时间曲线下面积、清除率、表观分布容积具有显著性差异,且差异具有统计学意义。采用Loo-Riegelman法计算累计吸收百分数。开始时空腹与餐后条件下药物吸收均较快,但在6h后,餐后条件下累计吸收百分数基本不再增加,而空腹条件下5h后一直在持续缓慢的吸收。结论进食对非洛地平的药代动力学参数有较大的影响,可以显著增加人体对非洛地平的吸收速度和程度。

ObjectiveTo study the effects of diet on the pharmacokinetic parameters of felodipine.MethodsFelodipine in plasma was determined by LC-MS/MS after oral administration of Felodipine Sustained-release Tablets under fasting and diet.The pharmacokinetic parameters and cumulative absorption percentage of felodipine were calculated under fasting and diet.ResultsPharmacokinetic parameters were calculated by non-compartmental analysis.The peak plasma concentrations (C max ) of fasting group and diet group were (1.57±0.83) and (5±2.36) ng·mL^-1 ,respectively;Area under the plasma concentration-time curve from time zero(pre-dose) to the 60 h concentration (AUC 0~60 ) were (19.56±10.18),(31.49±9.91) h·ng·mL^-1 ,respectively.The AUCs from time zero to infinity (AUC 0~∞) were (21.98±11.53),(34.1±10.97) h·ng·mL^-1 .Apparent elimination half-lives (t 1/2 ) were (19.52±7.3),(22.08±6.74)h,respectively.The time to C max (T max ) values were (4.12±2.26),(4.17±1.13)h,respectively.Clearance rates (CL) were (290.53±149.81),(161.33±51.7)L·h^-1 ,respectively.The apparent volumes of distribution (V z ) were (7 453.92±2 994.86),(5 006.18±1 828.22)L,respectively.C max ,AUC 0~60 ,AUC 0~∞,Cl,V z of fasting group were significantly different from diet group.The accumulated absorption percentage (Fa) was calculated by the equation of Loo-Riegelman.The absorbed speed of fasting group and diet group was rapidly.The cumulative absorption percentage of fed group was hardly increased during 6 h to 24 h after administration.The cumulative absorption percentage of fasting group was sustained and slow increase during 5 h to 24 h after administration.Drug was not completely absorbed within 24 hours.ConclusionDiet had a great influence on the absorption and metabolism of felodipine which can significantly increase the absorption rate and amount of felodipine.