新型天然酪氨酸酶抑制剂UP302乳膏的大鼠透皮吸收和排泄研究

目的: 研究新型天然酪氨酸酶抑制剂UP302乳膏经皮给予大鼠后的吸收和排泄。 方法: 大鼠经皮给予10 mg·cm^-2 UP302乳膏(以UP302计为0.2 mg·cm^-2),收集血液、尿液、粪便和皮肤生物样品,用LC-MS/MS法测定UP302浓度,HPLC法测定乳膏中未吸收的UP302量。大鼠尾静脉同时给予5 mg·kg^-1 UP302用于计算经皮给药的绝对生物利用度。 结果: UP302乳膏绝对生物利用度为8.07%,皮肤中UP302的量为透皮给药量的0.087%±0.025%,粪便中UP302排泄量为透皮给药量的0.091%±0.026%,尿液中未发现UP302,皮肤上残留的UP302量为78.96%±5.88%。 结论: 为评价UP302乳膏在动物体内的吸收动力学及为毒性安全性评价提供参考。

Objective: To investigate percutaneous absorption and excretion of a novel natural tyrosinase inhibitor UP302 emulsion applied to rats. Methods: Samples of blood,urine,feces and treated skin were collected after the emulsion was applied to rats at a dose of 10 mg·cm^-2(equivalent to 0.2 mg·cm^-2 of UP302) in which the contents of UP302 were determined by LC-MS/MS,and the residual UP302 on the skin surface of rats was measured by HPLC.Absolute bioavailability of UP302 which was injected in rats via the tail vein by 5 mg·kg^-1 was calculated. Results: Absolute bioavailability of UP302 emulsion was 8.07%,and the contents of UP302 in skin,feces and urine were 0.087%±0.025%,0.091%±0.026% and 0 of the applied dose,respectively.Residual amount of UP302 on the surface of skin was 78.96%±5.88%. Conclusion: Useful information was obtained for pharmacokinetics and safety evaluation of UP302 emulsion in rats.

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