PHARMACOKINETIC STUDY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 观察单剂量度他雄胺(2、3、4 mg)给药后第1、3、7、14、21、28天对5a-还原酶(5AR)活性的抑制作用，并测定血中3a-雄烷二醇葡萄糖醛酸苷(3a-diolG)水平及双氢睾酮(DHT)与睾酮的比值。为了实现这一目标，将采用开放标签的受试者间剂量比较研究设计，受试者接受2、3或4毫克的剂量。受试者(最多40人登记，至少允许24名完成者)将被随机分配到3个剂量水平中的一个。这项研究的结果将为随后的安慰剂对照、受试者内、度他雄胺对酒精影响的交叉研究提供剂量选择的依据。这项研究的第二个目的是研究I5AR基因的遗传变异与基线DHT/T比值的相关性以及在第3天服用度他雄胺的效果。该基因的一个变异被报道与较高的基线DHT水平有关，该基因的产物是度他雄胺的靶标之一。

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. To monitor the inhibition of 5a-reductase (5AR) enzyme activity at 1, 3, 7, 14, 21 and 28 days following administration of a single dose of dutasteride (2, 3, or 4 mg) by measuring the change in blood levels of 3a-androstanediol glucuronide (3a-diolG) and the ratio of dihydrotestosterone (DHT) to testosterone. To accomplish this aim, an open-label, between-subjects dose comparison study design will be employed with subjects receiving a 2, 3, or 4 mg dosage. Subjects (up to n=40 enrolled to allow a minimum of 24 completers) will be randomly assigned to one of the 3 dose levels. Results of this study will inform the dose selection for a subsequent placebo-controlled, within-subject, crossover study of dutasteride on the effects of alcohol. A secondary aim of this study is to examine the correlation of a genetic variation in the type I 5AR gene and baseline DHT/T ratio and effect of dutasteride at day 3. A variation in this gene, whose product is one of the targets of dutasteride, has been reported to be associated with higher baseline levels of DHT.