NORMATIVE AMBULATORY BLOOD PRESSURE IN BLACK ADOLESCENTS

丙磺舒对降压药氯沙坦及其E-3174代谢物尿排出的影响这项研究的假设是，氯沙坦及其代谢废物E-3174的分泌提供了一条主要的消除途径。氯沙坦对尿酸排泄的影响也可能与氯沙坦对近端肾小管的处理有关。丙磺舒是一种肾脏转运的抑制剂，它应该阻止氯沙坦和E-3174的分泌，并改变尿酸的排泄。本研究的具体目的是：1)确定在服用和不服用丙磺舒的情况下，药物氯沙坦和E-3174在人体内的代谢、分布、吸收和排泄方式；2)确定在服用丙磺舒和不服用丙磺舒的情况下，尿酸在洛沙坦中的排泄规律；3)进一步了解服用氯沙坦过程中早期钾排泄的特点；以及4)确定同样接受氯沙坦治疗并对血尿酸产生预期影响的受试者的血尿酸循环模式。这项研究的志愿者将是45岁以下的男性或女性。受试者将接受正常的筛查检查、筛查化学检查和血液学检查，并且不需要慢性药物治疗。女性受试者的怀孕测试将呈阴性。在研究开始之前，志愿者将被指示食用一种特殊的饮食，该饮食将持续72小时。在研究开始的前一天，将采集24小时尿样。志愿者将被随机分成四个不同的治疗组，每个组都有不同剂量的药物或安慰剂。在研究期间，将食用预定的饭菜。受试者在服药前和服药后两小时将被给予8盎司水饮用，以方便排尿和尿液收集。这项研究将需要在八周的时间内分别住院四个昼夜，在此期间将采集多个血液和尿液样本。每次24小时住院之后，研究的24小时门诊部分将继续收集尿液。

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.