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褪黑素缓释片的制备及其药代动力学研究

何仲贵*, 张天虹, 唐星, 张汝华   

  1. 沈阳药科大学药剂教研室, 沈阳 110016
  • 收稿日期:2003-01-23 修回日期:2003-05-10 出版日期:2003-06-15 发布日期:2003-06-15
  • 通讯作者: 何仲贵*

Preparation and Pharmacokinetic Characterization of Sustained Release Melatonin Tablet

HE Zhong-gui*, ZHANG Tian-hong, TANG Xing, ZHANG Ru-hua   

  1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
  • Received:2003-01-23 Revised:2003-05-10 Online:2003-06-15 Published:2003-06-15
  • Contact: HE Zhong-gui*

摘要: 目的 研制褪黑素HPMC骨架缓释片.并且研究缓释片的药物动力学及生物利用度. 方法 HPMC为骨架制备褪黑素缓释片. 考察褪黑素的颗粒大小, 片剂中HPMC的种类及含量, 片剂大小, 填充物的种类及数量, 压片力等影响药物释放度的因素.采用HPLC荧光检测器测定家犬静脉注射及口服褪黑素后的血药浓度. 结果 褪黑素静脉注射后体内血药浓度符合双隔室模型.静注两种剂量后AUC与剂量成正比, 生物半衰期分别为67.7分和84.6(P>0.05).褪黑素缓释片相对于常释胶囊的生物利用度为83.8%.缓释片及常释胶囊的绝对生物利用度分别为3.75%4.49%. 结论 褪黑素缓释片具有良好的缓释特性. 褪黑素缓释片及常释胶囊的绝对生物利用度都较低, 缓释片的生物利用度低于常释胶囊但体内平均滞留时间显著长于常释胶囊. 缓释片的体外释放与体内吸收速度有良好的相关性.

关键词: 褪黑素, HPMC, 缓释片, 生物利用度, 药物动力学

Abstract: Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t1/2β of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.

Key words: melatonin, melatonin, HPMC, HPMC, sustained release tablet, sustained release tablet, bioavailability, bioavailability, pharmacokinetics, pharmacokinetics

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Supporting: *Correesponding author. Tel.: 86-24-23843711-3703; fax: 024-23923591