马来酸罗格列酮脉冲型小片胶囊在家犬体内的药物动力学考察Pharmacokinetics of rosiglitazone maleate pulsatile mini-tablet capsules in dogs
赵秀丽,邹艳霜,赵秀峰,陈大为
ZHAO Xiu-li1,ZOU Yan-shuang1,ZHAO Xiu-feng2,CHEN Da-wei1 (1.School of Pharmacy
摘要(Abstract):
目的建立测定马来酸罗格列酮脉冲小片胶囊家犬体内马来酸罗格列酮含量的荧光检测HPLC方法,并应用于药物动力学研究。方法采用RP-HPLC法。色谱柱:ODS色谱柱;流动相:50 mmol.L-1乙酸胺水溶液(用冰醋酸调节pH 6)-乙腈(体积比50∶50);流速:1 mL.min-1;激发波长:320 nm,发射波长:370 nm;柱温:室温。结果马来酸罗格列酮、甲磺酸多沙唑嗪的保留时间分别为4.8、6.1 min;脉冲小片胶囊给药后分别在1、6、11 h出现3次释药高峰;tmax分别为1、6、11 h,ρmax分别为124.6、111.2、134.4μg.L-1。结论该方法灵敏、快速、准确,操作简便,线性范围宽,可用于马来酸罗格列酮的体内药物动力学研究。
Objective To develop a sensitive and specific HPLC method for determination of rosiglitazone maleate in dog plasma and provide a research method for pharmacokinetic investigation.Methods The HPLC method was used in the experiment.The mobile phase consisted of 50 mmol·L-1 ammonium acetate(pH=6)-acetonitrile(V∶V=50∶50).HPLC was run at the flow rate of 1.0 mL·min-1 and detected by fluorescence absorption at the excitation wavelength of 320 nm as excitation wave and the emission wavelength of 370 nm as emission wave at room temperature.Retention time of rosiglitazone maleate and internal standard were 4.8,6.1 min,respectively.Results After the administration of mini-tablet capsules,the maximum plasma levels were reached at the time of 1,6 and 11 h,respectively.The t1/2 and ρmax of the mini-tablet capsules were 1,6,11 h and 124.6,111.2,134.4 μg·L-1,respectively.The relative bioavailability of the mini-tablet capsules versus the marketed conventional tablets was 100.0%.Conclusions The established method is proved to be sensitive,rapid and accurate.It is suitable for clinical pharmacokinetic investigation of rosiglitazone maleate.
关键词(KeyWords):
血药浓度;马来酸罗格列酮;荧光检测高效液相色谱法
pharmacokinetics;rosiglitazone maleate;fluorescence HPLC method
基金项目(Foundation):
作者(Author):
赵秀丽,邹艳霜,赵秀峰,陈大为
ZHAO Xiu-li1,ZOU Yan-shuang1,ZHAO Xiu-feng2,CHEN Da-wei1 (1.School of Pharmacy
参考文献(References):
- [1]张军,陆彬.脉冲式给药系统的研究进展[J].国外医药:合成药生化药制剂分册,1998,19(5):317-319.
- [2]POSSI F,FORHANI P,GAZZANIGA A,et al.Thetime clock system:A new oral dosage form for fast andcomplete release of drug after a predetermined lag time[J].J Controlled Release,1994,31(1):99-108.
- [3]HATA T,SHIMAZAKI Y,KAGAYAMA A,et al.Development of a novel drug delivery system,time con-trolled explosion system(TES):Ⅴanimal pharmaco-dynamic study and human bioavailability study[J].In-ternational J of Pharmaceutics,1994,110(5):1-8.
- [4]CONTE U,MAGGI L,TORRE M L,et al.Press-coated tablets for time-programmed release of drugs[J].Biomaterials,1993,14(2):1017-1023.
- [5]OTSUKA M,MATSUDA Y.Controlled release ofhighly water-soluble pentoxifylline from time-time dis-integration-type wax matrix tablets[J].Pharmaceuti-cal Research,1994,11(2):351-357.
- [6]范田园,王杰,魏树礼.阿司匹林包衣脉冲片剂的研究[J].北京医科大学学报,2000,32(3):232-234.
- [7]齐美玲,王鹏,郑俊民,等.盐酸尼卡地平定时释放片研究[J].药学学报,1999,34(9):710-715.
- [8]LIN San-yang,LIN Kun-ghsu,LIN Mei-jane.Mi-cronized ethylcellulose used for designing a directlycompressed time-controlled disintegration tablet[J].JControlled Release,2001,70(6):321-325.
- [9]邹豪,蒋雪涛,郭涛.盐酸维拉帕米脉冲控释片的理化性质研究[J].解放军药学学报,2000,10(5):236-239.
- [10]BINNS J,STEVE H,MEWEN J,et al.The tolerabili-ty of multiple oral doses of pulsincap capsules inhealthy volunteers[J].J Controlled Release,1996,38(8):151-157.
- [11]郝钦,岗艳云,朱家壁.硝酸异山梨酯脉冲控释微丸的研制[J].中国医药工业杂志,1999,30(3):109-112.
- [12]赵圣印.糖尿病治疗药物的研究进展[J].国外医药:合成药生化药制剂分册,1999,20(3):130-135.
- [13]邹艳霜,陈大为.马来酸罗格列酮脉冲型小片胶囊的研制[J].沈阳药科大学学报,2002,19(4):235-239.
- [14]魏淑香,张振清.反相高效液相色谱法测定血浆中罗格列酮的含量[J].药物分析杂志,2001,21(5):365-366.
- [15]ANN-MARIE M,SUSAN F,PAUL R.Automatedhigh-performance liquid chromatography method forthe determination of rosiglitazone in human plasma[J].Journal of Chromatography B,2001,752(1):77-84.