盐酸吡格列酮四种晶型的大鼠体内药动学研究

目的：通过研究盐酸吡格列酮四种晶型在SD大鼠体内药动学和生物利用度,评价其优势药用晶型,为药物晶型物质状态对临床用药影响提供科学依据.方法：SD大鼠灌胃给予不同晶型盐酸吡格列酮固体原料药,采用高效液相色谱法测定盐酸吡格列酮血药浓度,非房室模型计算其大鼠体内药动学参数并在不同晶型之间进行比对.结果：大鼠经口给予盐酸吡格列酮四种晶型（晶Ⅰ、Ⅱ、Ⅲ及Ⅳ型）后,血液中的Cmax分别为（40.925±18.601）,（21.909±7.169）,（45.064±7.842）,（21.767±7.439） mg·L-1;Tmax分别为（3.417±3.787）,（4.417±3.323）,（1.333±0.876）,（7.417±2.836） h;AUC（0-i）分别为（290.828±80.22）,（208.192±96.745）,（355.433±74.683）,（267.243±100.584） mg·h·L-1.结论：经one-way ANO-VA统计学分析,大鼠口服不同晶型盐酸吡格列酮后,Cmax存在差异,晶Ⅲ型Cmax与晶Ⅱ型和晶Ⅳ型相比具有明显优势（P＜0.05）,其AUC（0-t）也明显优于晶Ⅱ型（P＜0.05）,血药浓度维持时间更长,其可能为优势药用晶型.

Study on Pharmacokinetics of Four Crystal Forms of Pioditazone Hydrochloride in Rats

Objective： To study the pharmacokinetics of four crystal forms of pioditazone hydrochloride in rats. Methods： Totally 36 rats were divided into 4 groups with oral administration of four different crystal forms of pioditazone hydrochloride. The plasma con- centrations were determined by HPLC. The pharmaeokinetic parameters were calculated. Results： After a single oral dose, the peak plasma concentration （Cmax） of pioditazone hydrochloride with crystal form I , Ⅱ, Ⅲ and IV was （40.925 ± 18. 601 ）, （21. 909 ± 7. 169）, （45. 064 ±7. 842） and （21. 767 ±7.439） mg · L-1; the peak time （t max） was （3. 417 ±3. 787）, （4. 417 ±3. 323）, （1. 333 ± 0. 876） and （ 7.417 ± 2. 836） h ; the area under curve （ A UC（0-1） ） was （ 290.828 ± 80.22）, （ 208.192 ± 96. 745 ）, （ 355. 433 ± 74.683） and （267. 243 ± 100. 584）mg · h · L-1, respectively. Conclusion： There are significant differences in blood concentration among the different crystal forms of pioditazone hydrochloride. Compared with that of the other crystal forms, the plasma concentration of crystal form Ⅲ is higher with longer maintenance time. Crystal form In of pioditazone hydrochloride is a promising choice for medi- clne