目的 以枸櫞酸鉀顆粒劑為對(duì)照，評(píng)價(jià)枸櫞酸鉀緩釋片在人體內(nèi)的藥動(dòng)學(xué)特征。方法 采用LC-MS方法，測(cè)定單次劑量（32名）和多劑量（20名，雙交叉試驗(yàn)）口服枸櫞酸鉀緩釋片和顆粒劑后尿樣中枸櫞酸根濃度，以內(nèi)源性藥物的基線校正，尿藥累積排泄量（Ae 0-24 h）和最大尿藥排泄速率（Rmax）為主要指標(biāo)計(jì)算其藥動(dòng)學(xué)參數(shù)，經(jīng)劑量校正進(jìn)行方差分析和對(duì)數(shù)轉(zhuǎn)化生物等效性原理分析后評(píng)價(jià)緩釋片的緩釋特征。結(jié)果 單次給藥后，受試藥的低、中、高（1.08、2.16、4.32 g）劑量組的Ae 0-24 h與對(duì)照藥（2.9 g）的Ae 0-24 h相比較差異無統(tǒng)計(jì)學(xué)意義；受試藥的低、中、高劑量組的Rmax與對(duì)照藥的Rmax相比較差異有統(tǒng)計(jì)學(xué)意義（P＜0.05）；多次給藥后結(jié)果顯示中劑量組的受試藥和對(duì)照藥的Ae 0-24 h差異無統(tǒng)計(jì)學(xué)意義，而低劑量組的受試藥和對(duì)照藥的Rmax差異顯著（P＜0.001）。結(jié)論 枸櫞酸鉀緩釋片與枸櫞酸鉀顆粒劑相比具有明顯的緩釋藥動(dòng)學(xué)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.

廣東省技術(shù)創(chuàng)新項(xiàng)目（2007915114）