NORMATIVE AMBULATORY BLOOD PRESSURE IN BLACK ADOLESCENTS

丙磺舒对氯沙坦（一种控制高血压的药物）及其E-3174代谢产物尿消除的影响的评价。本研究的假设是，氯沙坦及其代谢废物E-3174的分泌提供了主要的消除途径。氯沙坦对尿酸排泄的影响也可能与氯沙坦的近端肾小管处理有关。丙磺舒是一种肾转运抑制剂，可阻断氯沙坦和E-3174的分泌，并改变尿液中尿酸的排泄。本研究的具体目标是：1）确定在正常志愿受试者中，在有和没有丙磺舒的情况下，身体代谢、分布、吸收和排泄药物氯沙坦和E-3174的方式，2）确定在有和没有丙磺舒给药的情况下，尿酸对氯沙坦的尿液消除曲线，3）为了进一步表征伴随氯沙坦给药的钾的早期排泄，和4）确定安慰剂治疗的受试者中血清尿酸的周期性模式，所述受试者也接受氯沙坦治疗，其对血清尿酸具有预期的作用。本研究的志愿者为45岁以下的男性或女性。受试者的筛选检查、筛选生化和血液学检查均正常，不需要长期用药。女性受试者的妊娠试验结果为阴性。在研究开始前，将指导志愿者食用特殊饮食72小时。 在研究开始前一天，将采集24小时尿样。志愿者将被随机分为四个不同的治疗组，每个治疗组使用不同剂量的药物或安慰剂。研究期间将进食预先确定的膳食。在给药前和给药后2小时，将给予受试者8盎司水饮用，以促进排尿和尿液收集。本研究将需要在8周的时间跨度内住院4天4夜，在此期间将采集多份血液和尿液样本。 每次24小时住院治疗后，将进行研究的24小时门诊部分，其中将继续收集尿液。

An evaluation of the effect of probenecid on the urinary elimination of losartan , a drug to control high blood pressure, and its E-3174 metabolite. The hypothesis of this study is that the secretion of losartan and its metabolic waste, E-3174, provides a major route of elimination. The effect of losartan on the excretion of uric acid may also be linked to losartan's proximal tubular handling. Probenecid, an inhibitor of renal transport, should block the secretion of losartan and E-3174 as well as alter the excretion of uric acid in the urine. The specific aims of this study are; 1) to determine the way the body metabolizes, distributes, absorbs, and excretes the drug losartan and E-3174 with and without probenecid in normal volunteer subjects, 2) To define the urine elimination profile of uric acid to losartan with and without the administration of probenecid, 3) to further characterize the early excretion of potassium which attends the administration of losartan, and 4) to determine the cyclical pattern of serum uric acid in placebo-treated subjects who are also subjected to losartan therapy with its expected effect on serum uric acid. The volunteers for this study will be men or women below the age of 45 years. The subjects will have had normal screening exams, screening chemistries, and hematology panels, and will not be requiring medication on a chronic basis. Female subjects will have negative pregnancy tests. Before the start of the study, volunteers will be instructed to eat a special diet to be consumed for 72 hours. On the day before the onset of the study, a 24-hour urine sample will be taken. Volunteers will be randomized into four different treatment groups, each with a different dose of medications or a placebo. Predetermined meals will be consumed during the study. Subjects will be given 8 ounces of water to drink before dosing and at two hours after dosing to facilitate urination and urine collection. The study will require hospitalization for four separate days and nights over an eight-week time span, during which time multiple blood and urine samples will be obtained. Each 24-hour hospitalization will be followed by a 24-hour outpatient portion of the study, where urine will continue to be collected.