酮洛芬前体药物皮肤渗透代谢的立体选择性研究

Studies on the Stereoselectivity in Transdermal Permeation and Metabolism of Ketoprofen Prodrugs

目的 :研究酮洛芬前体药物 (酮洛芬甲酯、乙酯和异丙酯 )经离体SD大鼠皮肤渗透代谢的立体选择性 ,为利用前体药物方法促进透皮吸收提供依据。方法 :Valia Chien水平扩散池上进行大鼠皮肤渗透代谢研究。应用α 酸性糖蛋白手性柱 (AGP)拆分、测定透皮接受液中酮洛芬对映体的含量。结果 :消旋酮洛芬经离体SD大鼠皮肤渗透没有选择性 ,但其稳态渗透速率显著小于S 酮洛芬的稳态渗透速率 (P <0 0 5 )。酮洛芬前体药物经离体SD大鼠皮肤渗透被完全代谢成酮洛芬 ,其稳态形成速率大于酮洛芬本身经皮渗透的速率 (P <0 0 5 ) ,且所形成的酮洛芬具有立体选择性。结论 :酮洛芬前体药物能够促进酮洛芬的透皮吸收 ,其经皮渗透代谢具有立体选择性。

AIM:To study stereoselectivity in permeation and metabolism of ketoprofen prodrugs via excised rat skin.METHOD:Valia-Chien horizontal diffusion cells were used for permeation and metabolism studies in vitro.The concentrations of enantiomer in the receiver solution were assayed by HPLC using α-acidic glycoprotein chiral column.RESULT:The permeation of ketoprofen racemate didn't show stereoselectivity via excised rat skin,but its steady state permeation rate was lower than that of S-ketoprofen(P<0.05).Ketoprofen prodrugs were entirely metabolized to ketoprofen via excised SD rat skin.The steady state permeation and metabolism rate of prodrugs was higher than that of ketoprofen itself(P<0.05),and the metabolized ketoprofen showed stereoselectivity.CONCLUSION:Ketoprofen prodrugs can enhance the permeation of ketoprofen,and shows stereoselectivity in percutaneous permeation and metabolism.