沙利度胺多晶型大鼠体内药代动力学研究

Study on pharmacokinetics of thalidomide polymorphs in rats

目的研究沙利度胺3种晶型在SD大鼠胃肠道吸收过程,评价其优势药物晶型,探讨药物晶型状态对临床用药的影响。方法 SD大鼠灌胃给予不同晶型沙利度胺固体原料,采用高效液相色谱法测定血浆沙利度胺浓度,计算其大鼠体内药动学参数并在不同晶型之间进行对比。结果大鼠经口给予沙利度胺晶型α、晶型β和晶型γ后,血液中Cmax分别为6.79、4.28和5.55 mg.L-1,晶型α的测定值最大;Tmax分别为8.33、8.00和7.33 h;达峰时间相差约1 h;AUC0→t分别为40.73、30.34和38.74 mg.h.L-1,最大差距约25%;T12分别为2.29、1.95和1.93 h。结论大鼠口服不同晶型沙利度胺后血药浓度存在差异,其中晶型α峰浓度最高,血药浓度维持时间长。

Aim To study the gastrointestinal absorption process of thalidomide polymorphs in SD rats thus to find out the optimal crystal form and explore the factors that may affect the clinical effects of thalidomide. Method Each rat was intragastrically given one of three crystal forms of thalidomide. In plasma concentration of thalidomide were determined by HPLC method. The pharmacokinetic parameters were calculated and compared among polymorphs. Result The main pharmacokinetic parameters of thalidomide form α, βand γ were as follows; Cmax mg·L-1 ; Tmax were 8.33, 40.73, 30. 34 and 38.74 were 6. 79, 4. 28 and 5.55 8.00 and h; AUC0→1, were 40.73,30.34 and 38.74mg·h· L-1; T1/2 were 2 2.29, 1.95 and 1.93 h, respectively. Conclusion Thalidomide form α has the highest peak concentration and its plasma concentration is maintained for a longer time than others.