目的 以枸橼酸钾颗粒剂为对照，评价枸橼酸钾缓释片在人体内的药动学特征。方法 采用LC-MS方法，测定单次剂量（32名）和多剂量（20名，双交叉试验）口服枸橼酸钾缓释片和颗粒剂后尿样中枸橼酸根浓度，以内源性药物的基线校正，尿药累积排泄量（Ae 0-24 h）和最大尿药排泄速率（Rmax）为主要指标计算其药动学参数，经剂量校正进行方差分析和对数转化生物等效性原理分析后评价缓释片的缓释特征。结果 单次给药后，受试药的低、中、高（1.08、2.16、4.32 g）剂量组的Ae 0-24 h与对照药（2.9 g）的Ae 0-24 h相比较差异无统计学意义；受试药的低、中、高剂量组的Rmax与对照药的Rmax相比较差异有统计学意义（P＜0.05）；多次给药后结果显示中剂量组的受试药和对照药的Ae 0-24 h差异无统计学意义，而低剂量组的受试药和对照药的Rmax差异显著（P＜0.001）。结论 枸橼酸钾缓释片与枸橼酸钾颗粒剂相比具有明显的缓释药动学特征。

Objective To study the in vivo pharmacokinetic characteristics of Potassium Citrate Sustainded-release Tablets (PCSTs) in healthy volunteers, comparing with ordinary granules. Methods The concentration of folic acid group in urine was determined by LC-MS after a single dose (32 cases) or multiple doses (20 cases, the double cross test) oral PCSTs and granules, baseline was checked by endogenous drugs, pharmacokinetic parameters were calculated by urine drug cumulative excretion (Ae 0-24 h) and maximum urine drug excretion rate (Rmax) as key indicators. The sustainded release characteristics of PCSTs were evaluated after variance analysis and logarithmic transformation principle of bioequivalence analysis by dose-adjusted. Results The pharmacokinetic parameters of PCSTs and granules from the single-dose study were as follows: Ae 0-24 h of test drug (low-dose, 1.08 g), (mid-dose, 2.16 g), (high-dose, 4.32 g), and had no significant difference compared with 2.9 g of reference drugs. Rmax of test drug (low-dose, 1.08 g), (mid-dose, 2.16 g), (high-dose, 4.32 g) h, and had the significant differences compared with reference drugs (P<0.05). The pharmacokinetic parameters of PCSTs and granules from the multi-dose study were as follows: Ae 0-24 h of test drug (mid-dose, 2.16 g) and had no significant differences compared with reference drugs. Rmax of test drug and reference drug had significant differences (P<0.001). Results Compared with granules, PCSTs show the significant sustainded-release characteristics.

广东省技术创新项目（2007915114）