醋酸地塞米松和地塞米松磷酸钠的油水分配系数与其经皮渗透行为之间的相关性研究

A Study on the Relationship Between the Oil/Water Partition Coefficient and Transdermal Action of Drugs: Dexamethasone Acetate and Dexamethansone Sodium Phosphate

目的探讨脂溶性醋酸地塞米松和水溶性地塞米松磷酸钠的油水分配系数与其体外经皮渗透速率及体内皮下透过药物总量之间的相关性。方法采用了高效液相含量测定法测定醋酸地塞米松和地塞米松磷酸钠在不同pH环境中的油水分配系数,并采用改良型Franz扩散池装置通过体外透皮扩散实验得到两种药物的经皮渗透速率,更采用微透析技术通过将线性探针植入大鼠腹部皮下得到两种药物的体内皮下透过总量,再分别对醋酸地塞米松和地塞米松磷酸钠的上述三种参数进行相关性考察。结果在本实验研究的脂溶性及pH范围内,醋酸地塞米松的体外经皮渗透速率与油水分配系数的回归方程为Y=4.682-0.03X,r2=0.906,其体内皮下透过药物总量与油水分配系数的回归方程为Y=720.786-0.63X,r2=0.896,均具有良好的负相关性;地塞米松磷酸钠的体外经皮渗透速率与油水分配系数的回归方程为Y=7.923+3.393X,r2=0.939,其体内皮下透过药物总量与油水分配系数的回归方程为Y=21.324+14.558X,r2=0.875,均具有良好的正相关性。结论随着pH值的增加,醋酸地塞米松的油水分配系数有不断增加的趋势,其体外经皮渗透速率和体内皮下透过药物总量则成不断下降的趋势;而地塞米松磷酸钠的油水分配系数及其体外经皮渗透速率、体内皮下透过药物总量则随着pH值的增加而均不断减小。因此,两种不同脂溶性的地塞米松外用制剂的pH值或油水分配系数的增大(或减少)可能会对该两种药物的体外经皮渗透速率及体内皮下透过药物总量产生性质不同(增大或减少)的影响,从而对此两种药物经皮给药疗效的发挥也可能具有性质不同的影响作用。

OBJECTIVE Research the relevance between the oil/water partition coefficients and in vitro transdermal speed, the oil/water partition coefficients and the amount of drugs permeated through skin in vivo of fat-soluble dexamethasone acetate and water- soluble dexamethansone sodium phosphate. METHODS In this study, oil/water partition coefficients of dexamethasone acetate and dexamethansone sodium phosphate in different pH environment were determined by reversed phase high performance liquid chromatog- raphy, their in vitro transdermal speed were obtained via transdermal-absorption test with improved Franz diffusing cells and their the a- mount of drugs permeated through skin in vivo were calculated by microdialysis in which the linear probe was implanted in the dermis of the abnormal skin of rat. Then the relevance of above-mentioned three index of dexamethasone acetate and dexamethansone sodium phosphate were examinationed. RESULTS In the fat-soluble and pH range of our test, the relationship between oil/water partition co- efficients and in vitro transdermal speed of dexamethasone acetate and dexamethasone sodium phosphate followed a linear relationship, whose equation were Y = 4. 682 -0. 03X, r^2 = 0. 906 and Y = 7. 923 ＋ 3. 393X, r^2 = 0. 939, respectively. And the relationship between oil/water partition coefficients and the amount of drugs permeated through skin in vivo of dexamethasone acetate and dexamethasone so- dium phosphate also followed a linear relationship, whose equation were Y = 720. 786 -0. 63X,r^2 = 0. 896 and Y = 21. 324 ＋ 14. 558X, r^2 = 0. 875, respectively. CONCLUSION The oil/water partition coefficients of dexamethasone acetate increases along with the raise of its pH value, but its in vitro transdermal speed and the amount of drugs permeated through skin in vivo descend. On the other hand, when pH value increases, the oil/water partition coefficients, in vitro transdermal speed and the amount of drugs permeated through skin in vivo of dexamethasone sodium phosphate are all under a descent. Thus, we conclude that the pH value and oil/water partition coefficients of external preparation made with different liposolubility Dexamethasone may play a different role on the medicine curative effect.