ORAL ANDROGENS IN MAN-3: PK OF ORAL TESTOSTERONE BY ALPHA5-DUTASTERIDE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的： 本研究旨在评价睾酮（T）与度他雄胺（D）联合给药时口服给药的疗效，比较纳米研磨T（NmT+D）与溶于Capmul的T（CpT+D）。 研究方法： 12名正常男性在第-14天接受亮丙瑞林给药，以抑制内源性T生物合成。 受试者还在第-14天接受单次负荷剂量的D（24.5 mg），随后接受每日剂量（0.5 mg），持续24天。对于T治疗，受试者在第1天（空腹）接受200 mg CpT+D，第2天（空腹）接受400 mg CpT + D，第3天（进食）接受400 mg CpT + D。第二周，使用NmT+D重复该方案。测定血清T和双氢睾酮（DHT）：给药前，每次给药后0.5、1、2、3、4、6、8、10、12和24小时。 结果如下： 亮丙瑞林给药后2周，T水平低于正常范围。400 mg两种口服T+D制剂的平均血清T升高至正常范围下限以上，持续8-10小时。 在空腹状态下，CpT+D的AUC 0 -24和Cmax大于NmT+D。 食物对两种制剂的PK影响极小。在整个研究期间，两种制剂的血清DHT均低于正常范围。未观察到肝功能检查或其他不良事件的显著变化。 结论： 400 mg剂量的任一口服制剂使血清T正常化8-10小时并抑制DHT，证明口服T作为治疗男性性腺功能减退症的有希望的疗法的可行性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: This study was designed to evaluate the efficacy of oral delivery of testosterone (T) when co-administered with dutasteride (D), comparing nanomilled T (NmT+D) versus T dissolved in Capmul (CpT+D). Methods: Twelve normal men were administered leuprolide on Day -14 to suppress endogenous T biosynthesis. Subjects also received a single loading dose of D (24.5mg) on Day -14 followed by daily doses (0.5 mg) for 24 days. For T treatment, subjects were administered CpT+D, 200 mg on day 1 (fasted), 400 mg on day 2 (fasted), and 400 mg on day 3 (fed). The following week this regimen was repeated using NmT+D. Serum T and dihydrotestosterone (DHT) were measured: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours after each dose. Results: Two weeks after leuprolide administration T levels were below the normal range. Mean serum T was increased above the lower limit of the normal range for 8-10 hours with 400 mg of both formulations of oral T+D. In the fasting state, CpT+D exhibited a greater AUC0-24 and Cmax than NmT+D. Food had minimal effect on the PK of either formulation. Serum DHT remained below the normal range throughout the study period with both formulations. No significant changes in liver function tests or other adverse events were observed. Conclusions: A 400 mg dose of either oral formulation normalized serum T for 8-10 hours and suppressed DHT, demonstrating the feasibility of oral T as promising therapy for the treatment of male hypogonadism.