Danza G, Muratori M, Guarna A, Occhiato E G, Sadri R, Serio M
Clinical Physiopathology Department, University of Firenze, Italy.
J Steroid Biochem Mol Biol. 1993 Sep;46(3):373-9. doi: 10.1016/0960-0760(93)90227-n.
Pharmacokinetics of 4-hydroxyandrostenedione (4-OHA), a potent aromatase inhibitor under investigation for treatment of postmenopausal breast cancer, were studied using two formulations with different particle sizes of 4.2 and 8.0 microm, respectively. A single 250 mg dose of 4-OHA of each of the two formulations was administered in two different periods to six healthy male volunteers and blood samples were collected for up to 14 days. 4-OHA plasma levels were determined using the isotope dilution mass spectrometry method. Comparison of the pharmacokinetic profiles of the two formulations did not show any statistically significant difference, even though the 4.2 microm particle size gave apparently higher levels at 24 h. Using this formulation, the effects of 4-OHA on the plasma levels of aromatizable androgens (testosterone and androstenedione) and 17beta-estradiol were studied. An isotope dilution mass spectrometry method was developed for the simultaneous quantitative determination of these steroids in human plasma. The analysis of plasma samples showed a significant reduction of plasma estradiol concentrations (50%) which coincided with the maximum concentration peak of the inhibitor, whereas no significant changes in androgen levels were observed.
4-羟基雄烯二酮（4-OHA）是一种正在研究用于治疗绝经后乳腺癌的强效芳香化酶抑制剂，分别使用粒径为4.2微米和8.0微米的两种制剂对其药代动力学进行了研究。在两个不同时间段，给6名健康男性志愿者分别单次服用250毫克这两种制剂中的4-OHA，并采集血样长达14天。采用同位素稀释质谱法测定4-OHA的血浆水平。两种制剂药代动力学曲线的比较未显示出任何统计学上的显著差异，尽管粒径为4.2微米的制剂在24小时时的水平明显较高。使用该制剂，研究了4-OHA对可芳香化雄激素（睾酮和雄烯二酮）和17β-雌二醇血浆水平的影响。开发了一种同位素稀释质谱法用于同时定量测定人血浆中的这些甾体。血浆样本分析显示，血浆雌二醇浓度显著降低（50%），这与抑制剂的最大浓度峰值一致，而雄激素水平未观察到显著变化。
