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黄体酮混悬注射剂药动学及体内外相关性研究

刘兰岚, 蔡其霖, 张汶彦, 严真, 尹莉芳

刘兰岚,蔡其霖,张汶彦,等. 黄体酮混悬注射剂药动学及体内外相关性研究[J]. 中国药科大学学报,2024,55(2):217 − 223. DOI: 10.11665/j.issn.1000-5048.2023050801
引用本文: 刘兰岚,蔡其霖,张汶彦,等. 黄体酮混悬注射剂药动学及体内外相关性研究[J]. 中国药科大学学报,2024,55(2):217 − 223. DOI: 10.11665/j.issn.1000-5048.2023050801
LIU Lanlan, CAI Qilin, ZHANG Wenyan, et al. Pharmacokinetics and in vitro-in vivo correlation of progesterone suspension injection[J]. J China Pharm Univ, 2024, 55(2): 217 − 223. DOI: 10.11665/j.issn.1000-5048.2023050801
Citation: LIU Lanlan, CAI Qilin, ZHANG Wenyan, et al. Pharmacokinetics and in vitro-in vivo correlation of progesterone suspension injection[J]. J China Pharm Univ, 2024, 55(2): 217 − 223. DOI: 10.11665/j.issn.1000-5048.2023050801

黄体酮混悬注射剂药动学及体内外相关性研究

详细信息
    通讯作者:

    尹莉芳: Tel:025-83271018 E-mail:lifangyin_@163.com

  • 中图分类号: R944

Pharmacokinetics and in vitro-in vivo correlation of progesterone suspension injection

  • 摘要:

    探讨黄体酮混悬注射剂体外释放、体内药动学以及体内外相关性,以自制黄体酮混悬注射液为例,采用桨法和透析袋法测定3种不同粒径(3、5、7 μm)的黄体酮混悬注射剂的体外释放曲线;以SD大鼠为实验动物,研究3种粒径黄体酮混悬注射剂的体内药动学,并将血药浓度-时间曲线经Wagner-Nelson法处理后得到体内累积吸收曲线,与透析袋法所得体外累积释放曲线建立体内外相关性。结果表明,黄体酮混悬注射液采用桨法测定体外释放度时,20 min内均迅速释放85%以上,而采用透析袋法测定时分别在40、84、120 h达85%累积释放度。透析袋法所得体外释放趋势与体内释药趋势基本一致,相关系数大于0.95,具有较强的体内外相关性。本研究为长效混悬注射剂体内外相关性的建立提供参考。

    Abstract:

    To investigate the in vitro release, in vivo pharmacokinetics, and the in vitro-in vivo correlation of progesterone suspension injection, self-made progesterone suspension injection was taken as an example. The in vitro release curves of three different particle sizes of progesterone suspension injections were measured using paddle method and dialysis bag method. The in vivo pharmacokinetic characteristics of self-made progesterone suspension injection was studied on SD rats. The plasma concentration of self-made progesterone preparation was detected after intramuscular injection, and correlated with the in vitro release profiles obtained by the dialysis bag method after processing by Wagner-Nelson method. The results showed that when the in vitro release of three different particle sizes of progesterone suspension injections was measured by the paddle method, more than 85% was rapidly released within 20 min, while 85% cumulative release was reached at 40 h, 84 h and 120 h by dialysis bag method, respectively. The release rate obtained by the dialysis bag method was basically consistent with the in vivo release trend, with a correlation coefficient of >0.95, indicating a strong in vivo and in vitro correlation. This study provides some reference for the establishment of the in vitro and in vivo correlation of long-acting suspension injection.

  • Figure  1.   In vitro cumulative release curve of progesterone suspension injections (paddle method) ($ \bar{x}\pm s $, n=6)

    Figure  2.   In vitro cumulative release curve of progesterone suspension injections(dialysis bag method) ($ \bar{x}\pm s $, n=6)

    Figure  3.   Chromatograms of blank artificial plasma (A), artificial plasma including internal standard (B), blank rat plasma (C), rat plasma including internal standard (D), and rat plasma including progesterone (E)

    Notes:Blue line represents progesterone, Red line represents internal standard

    Figure  4.   Mean plasma concentration-time curves of progesterone suspension injections in SD rats ($ \bar{x}\pm s $, n=6)

    Figure  5.   Cumulative release curve in vivo of progesterone suspension injections ($ \bar{x}\pm s $, n=6)

    Figure  6.   In vivo and in vitro correlation of progesterone suspension injections

    A:3 μm;B:5 μm;C:7 μm

    Table  1   Pharmacokinetics parameters of progesterone in plasma after administration of three particle sizes of suspension injections ($ \bar{x}\pm s $, n=6)

    ParameterProgesterone suspension injections
    357 μm
    cmax/(ng/mL)108.83±10.9486.86±4.6553.14±4.66
    tmax/d1.02.54.0
    AUC0-t/(ng·h/mL)6807.64±791.607982.68±541.646191.22±333.09
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出版历程
  • 收稿日期:  2023-05-07
  • 刊出日期:  2024-04-24

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