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首页> 外文期刊>Biomedical Chromatography: An International Journal Devoted to Research in Chromatographic Methodologies and Their Applications in the Biosciences >Pharmacokinetics of aconitine in rat skin after oral and transdermal gel administrations
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Pharmacokinetics of aconitine in rat skin after oral and transdermal gel administrations

机译：口服和经皮凝胶给药后乌头碱在大鼠皮肤中的药代动力学

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摘要

The purpose of this study was to evaluate percutaneous penetration and arrhythmogenic effects of aconitine after transdermal administration, compared with the oral route. Skin penetration of aconitine was tested by a microdialysis technique in rats and in vivo recovery was determined by retrodialysis. After oral and transdermal administration of aconitine, dialysate was sampled at 20min intervals until the end of the experiment for the determination of concentration of aconitine in skin. Blood samples were collected and analyzed using a validated HPLC-MS/MS method. In addition, we concurrently recorded the electrocardiogram (ECG). The in vivo recovery of aconitine in the skin was calculated to be 39.59%. The C max values for aconitine absorbed into the skin after oral and transdermal administration were 1.51±0.53 and 2723.8±848.8ng/mL, respectively, and within the plasma, 215.86±79.29 and 20.92±3.15ng/mL. The C max value for the plasma concentration of aconitine after oral administration was approximately 10 times higher than with the transdermal route. For oral administration, the ECG revealed various types of arrhythmias at a period of T max, which is normal in transdermal gel administration. These results indicate that transdermal aconitine gel is a safe formulation that can deliver the drug in sufficient amounts and safe concentrations to produce therapeutic action in rats.
机译：这项研究的目的是评估与口服途径相比，乌头碱经皮给药后的经皮渗透和心律失常作用。乌头碱的皮肤渗透性通过微透析技术在大鼠中测试，体内恢复通过逆透析确定。在口服和经皮施用乌头碱之后，以20分钟的间隔取样透析液，直到实验结束以测定皮肤中乌头碱的浓度。收集血样并使用经过验证的HPLC-MS / MS方法进行分析。此外，我们同时记录了心电图（ECG）。乌头碱在皮肤中的体内回收率经计算为39.59％。口服和经皮给药后乌头碱吸收至皮肤的C max值分别为1.51±0.53和2723.8±848.8ng / mL，在血浆中为215.86±79.29和20.92±3.15ng / mL。口服后乌头碱的血浆浓度的C max值比经皮途径高约10倍。对于口服给药，ECG在T max期间显示出各种类型的心律不齐，这在经皮凝胶给药中是正常的。这些结果表明，经皮乌头碱凝胶剂是安全的制剂，可以以足够的量和安全的浓度递送药物以在大鼠中产生治疗作用。

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