摘要
目的研究利培酮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利培酮固体原料,采用高效液相色谱法测定血浆利培酮的浓度,计算其大鼠体内药动学参数并在不同晶型之间进行比对。结果大鼠经口给予利培酮晶型Ⅰ、晶型Ⅱ和晶型Ⅲ后,血液中利培酮ρmax分别为(2.93±1.37),(2.24±1.04)和(2.02±1.52)mg.L-1,晶型I的测定值最大;tmax分别为(1.17±0.80),(1.83±1.18)和(4.33±2.05)h,达峰时间相差3 h以上;AUC0→t分别为(5.81±2.10),(5.22±1.78)和(6.15±4.25)mg.h.L-1,最大差距约18%;t1/2分别为(0.71±0.11),(0.76±0.21)和(1.20±0.78)h。结论大鼠口服不同晶型利培酮后血药浓度存在差异,其中晶型Ⅰ血药浓度达峰时间最短,峰浓度最高;晶型Ⅲ达峰缓慢,但血药浓度维持时间长。
OBJECTIVE To study the gastrointestinal absorption process of risperidone polymorphs in SD rats thus to find out the optimal crystal form and explore the factors that may affect the clinical effects of risperidone. METHODS Each rat was intragastrically given one of three crystal forms of risperidone. The concentrations of resperidone in plasma were determined by HPLC method. The pharmacokinetics parameters were calculated and compared among polymorphs. RESULTS The main pharmacokinetic parameters of risperidone form Ⅰ , Ⅱ and Ⅲ were as follows ： ρmax were （2. 93 ± 1.37）, （2. 24 ±1.04） and （2. 02 ± 1.52 i mg .L- 1 ; tmax were （1.17±0.80）, （1.83±1.18） and （4.33±2.05） h; AUC0→t,were （5.81±2.10）, （5.22±1.78） and （6.15±4.25） mg.h. L-1 ; t1/3 were （0.71 ±0. 11）, （0.76 ±0.21） and （1.20 ±0.78） h, respectively. CONCLUSION Risperidone form I reaches peak concentration first and has the highest peak concentration. Form m is absorbed slowly, but its plasma concentration is maintained for a long time.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2011年第24期1919-1922,共4页
Chinese Pharmaceutical Journal
基金
卫生部公益性行业科研专项(200902008)
重大新药创制科技重大专项(2009ZX09302-003
2009ZX09501-021)
