目的:研究枸橼酸他莫昔芬凝胶剂经大鼠乳腺组织周围皮肤局部给药后在大鼠体内组织的分布.方法:SD大鼠50只,随机分成实验组和对照组,各组25只大鼠.对照组按10 mg/kg的剂量灌胃给予枸橼酸他莫昔芬丙二醇溶液,实验组按50 mg/kg的剂量将枸橼酸他莫昔芬凝胶剂均匀涂布于大鼠乳腺组织周围.2组大鼠均每24 h给药1次,连续给药3 d,并于末次给药后0、4、8、12、24 h处死大鼠,剖取乳腺、肝脏、子宫及卵巢等组织,采用HPLC法测定不同组织中枸橼酸他莫昔芬的分布.结果:2组大鼠乳腺组织中枸橼酸他莫昔芬到达峰值时间均为4 h,各时间点实验组浓度均高于对照组(t=7.183、7.788、8.078、5.804和5.442,P均＜0.001);2组其他各组织不同时间点他莫昔芬浓度间差异无统计学意义(P＞0.05).结论:枸橼酸他莫昔芬凝胶剂经乳腺组织周围皮肤局部给药后可显著增加乳腺组织对药物的吸收.%Aim:To study the tissue distribution of tamoxifen after transdermal administration of tamoxifen citrate gel on the breast skin of rats. Methods:Fifty female rats were randomly allocated into 2 groups( 25 in each group ). Experiment group received transdermal tamoxifen citrate gel once per day at 50 mg/kg for 3 days, and control group received tamoxifen citrate solution at 10 mg/kg for 3 days. The rats were sacrificed at 0, 4, 8, 12, 24 h after the last administration. The concentrations of tamoxifen in breast, womb, ovary and liver were determined by HPLC. Results:Peak concentration ( Cmax ) of tamoxifen in breast of the two groups both occurred at 4 h following last administration. The Cmax of tamoxifen in breast of the experiment group was significantly higher than that in the control group at different time points( t = 7.183.7.788.8.078.5.804 and 5. 442,P <0.001 ). There was no significant difference in the concentration of tamoxifen from other tissue of the 2 groups at different time points( P > 0.05 ). Conclusion:Tamoxifen has more satiafactory distribut ion the breast tissue after transdermal administration of tamoxifen citrate gel compared with oral administration.
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