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盐酸西那卡塞片的体内外相关性研究
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| 篇名： | 盐酸西那卡塞片的体内外相关性研究 |
| TITLE： | |
| 摘要： | 目的：考察盐酸西那卡塞片的体外溶出行为和体内药动学过程，并进行体内外相关性（IVIVC）评价。方法：采用高效液相色谱法（HPLC），测定盐酸西那卡塞片在8种溶出介质[pH 1.2盐酸溶液、pH 2.0盐酸溶液、pH 4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液、水、人工胃液（SGF）、饱腹人工肠液（FeSSIF）、空腹人工肠液（FaSSIF）]中的累积溶出度（Q），并绘制溶出曲线。采用HPLC-质谱联用法测定盐酸西那卡塞片的血药浓度；选择12名健康男性受试者，在空腹或饱腹（高脂食物）状态下单剂量口服盐酸西那卡塞片75 mg，测定给药前（0 h）与给药后0.5、1、2、3、4、6、8、12、24 h时的血药浓度，并绘制平均血药浓度-时间曲线。采用DAS 3.0软件计算饱腹组受试者体内累积吸收百分数（F），并与该制剂相应时间点的体外Q值作线性回归，进行IVIVC评价。结果：盐酸西那卡塞片在8种溶出介质中的溶出曲线存在较大差异；空腹组和饱腹组受试者的AUC0→t、AUC0→∞和cmax组间比较，差异均有统计学意义（P＜0.05），表明高脂食物对该制剂的体内药动学过程有明显影响；该制剂在饱腹组受试者体内的F值与其体外在FeSSIF中的Q值的相关系数最高（0.977 9），表明存在良好的IVIVC（A级）。结论：盐酸西那卡塞片在FeSSIF中（桨法，50 r/min）的体外溶出行为与其体内药动学过程存在良好的相关性，可用于预测该制剂在体内的释放和吸收情况。 |
| ABSTRACT： | OBJECTIVE： To investigate the in vitro dissolution behavior and in vivo pharmacokinetics of Cinacalcet hydrochloride tablets， and to evaluate its in vivo-in vitro correlation （IVIVC）. METHODS： HPLC method was adopted to determine the accumulative dissolution（Q） of Cinacalcet hydrochloride tablets in 8 kinds of medium [pH 1.2 hydrochloric acid solution， pH 2.0 hydrochloric acid solution， pH 4.5 acetate buffer solution， pH 6.8 phosphate buffer solution， water， artificial gastric fluid （SGF）， full belly artificial intestinal fluid （FeSSIF）， fasting artificial intestinal fluid （FaSSIF）]， and the dissolution curves were drawn. HPLC-MS method was used to determine the blood concentrations of Cinacalcet hydrochloride tablets. A total of 12 healthy male volunteers were selected and given single oral dose of Cinacalcet hydrochloride tablets 75 mg under the state of fasting or satiety （high-fat food）. The blood concentration of cinacalcet hydrochlorid was determined before medication （0 h） and 0.5， 1， 2， 3， 4， 6， 8， 12， 24 h after medication. Average blood concentration-time curves were drawn. The in vivo accumulative absorption percentage （F） of satiety group was calculated by using DAS 3.0 software. Linear regression of F with in vitro Q was carried out to analyze its IVIVC. RESULTS： There was great difference among dissolution curves of Cinacalcet hydrochloride tablets in 8 kinds of dissolution mediums. There were differences of AUC0→t， AUC0→∞ and cmax between fasting group and satiety group， with statistical significance （P＜0.05）， showing high-fat food had significant effect on in vivo pharmacokinetics. Correlation coefficient of in vivo F in satiety group with in vitro Q of the tablets in FeSSIF was highest （0.977 9）， manifesting good IVIVC （class A）. CONCLUSIONS： The in vitro dissolution behavior of Cinacalcet hydrochloride tablets in FeSSIF （paddle method，50 r/min） is well associated with its in vivo pharmacokinetics， which can be used for predicting in vivo dissolution and absorption of the tablets. |
| 期刊： | 2018年第29卷第12期 |
| 作者： | 吴晓雯，庞婕，孙增先 |
| AUTHORS： | WU Xiaowen，PANG Jie，SUN Zengxian |
| 关键字： | 盐酸西那卡塞片；溶出度；药动学；体内外相关性 |
| KEYWORDS： | Cinacalcet hydrochloride tablets； Dissolution； Pharmacokinetics； in vivo-in vitro correlation |
| 阅读数： | 626 次 |
| 本月下载数： | 23 次 |
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