大鼠来曲唑药代动力学的性别差异。

Gender difference in letrozole pharmacokinetics in rats.

作者信息

Liu X D, Xie L, Zhong Y, Li C X

机构信息

Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.

出版信息

Acta Pharmacol Sin. 2000 Aug;21(8):680-4.

PMID:11501174

Abstract

AIM

To study gender difference in letrozole (Letr) pharmacokinetics in rats.

METHODS

Letr concentrations in plasma and tissues were determined after ig administration of Letr 2 mg/kg. Recoveries of Letr in urine and feces were also analyzed.

RESULTS

Marked gender differences were found 6 h after ig Letr 2 mg/kg, the plasma concentrations of Letr in male rats were significantly (P < 0.01) lower than those in female rats. For example, at 24, 36, 48, and 72 h after administration, plasma concentrations in female rats were about 3.3, 5.6, 10.5, and 7.4-fold of that of male rats, respectively. AUC value of Letr in male was only about one-third of that in female rats. Estimated terminal phase half-lives (T1/2) were 10.5 and 40.4 h, respectively. In female rats, cumulative excreted fractions of Letr in urine and feces were 5.8% +/- 1.4% and 6.6% +/- 1.1% within 120 h after administration, respectively, but in male rats, the excreted fractions of Letr in urine and feces were only 1.30% +/- 0.59% and 0.87% +/- 0.31%. Letr concentrations in female rat tissues were significantly (P < 0.01) higher than those in male rat tissues 24 h after administration.

CONCLUSION

There are marked gender differences in Letr pharmacokinetics in rats.

摘要

目的

研究来曲唑（Letr）在大鼠体内药代动力学的性别差异。

方法

给予大鼠2 mg/kg来曲唑灌胃后，测定血浆和组织中来曲唑的浓度。同时分析来曲唑在尿液和粪便中的回收率。

结果

给予2 mg/kg来曲唑灌胃6小时后发现明显的性别差异，雄性大鼠血浆中来曲唑浓度显著低于雌性大鼠（P<0.01）。例如，给药后24、36、48和72小时，雌性大鼠血浆浓度分别约为雄性大鼠的3.3、5.6、10.5和7.4倍。雄性来曲唑的AUC值仅约为雌性大鼠的三分之一。估计终末相半衰期（T1/2）分别为10.5和40.4小时。在雌性大鼠中，给药后120小时内来曲唑在尿液和粪便中的累积排泄分数分别为5.8%±1.4%和6.6%±1.1%，但在雄性大鼠中，来曲唑在尿液和粪便中的排泄分数仅为1.30%±0.59%和0.87%±0.31%。给药24小时后，雌性大鼠组织中来曲唑浓度显著高于雄性大鼠组织（P<0.01）。