PK OF SILYBIN-PHOSPHATIDYLCHOLINE COMPLEX (SILIPHOS) IN DIABETIC NEPHROPATHY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。目的：描述单次给药和持续摄入（1周）Siliphos后，伴有和不伴有肾脏受累的II型糖尿病患者中Siliphos的药代动力学特征。 研究方法：需要36名诊断为II型糖尿病的受试者。他们将根据肾脏疾病的严重程度分为三组：12名无肾脏疾病证据的患者，12名患有III期慢性肾脏疾病的患者和12名患有IV期慢性肾脏疾病的患者。受试者将接受7次研究访视（筛选、药代动力学住院访视1、2次门诊访视（住院访视后24和48小时）、药代动力学住院访视2、2次门诊访视（住院访视后24和48小时））。首次住院访视将确定Siliphos初治患者的单次给药药代动力学。第二项研究将记录常规剂量Siliphos 160 mg po bid给药1周后的稳态动力学。两次测试之间将间隔2至4周。药代动力学检测将包括在Audie L的一般临床研究中心（GCRC）住院25小时期间采集血液和尿液。Murphy VA医院（ALMVAH），随后在出院后24小时和48小时进行两次门诊访视。血液和尿液样本也在门诊就诊时采集。 临床相关性：Siliphos是一种有效的抗氧化剂，可以防止肾脏损伤，减少糖尿病患者的胰岛素抵抗和纠正脂质异常。

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: To characterize the pharmacokinetics of Siliphos in individuals with type II diabetes mellitus with and without renal involvement following both single dose and sustained intake (one week) of Siliphos. RESEARCH PLAN and METHODS: Thirty-six subjects diagnosed with type II diabetes mellitus will be required. They will be divided in three groups based on severity of renal disease: 12 without evidence of renal disease, 12 with stage III chronic kidney disease and 12 with stage IV chronic kidney disease. Subjects will have 7 study visits (screening, pharmacokinetic inpatient visit 1, 2 outpatient visits (24 and 48 hours following the inpatient visit), pharmacokinetic inpatient visit 2, 2 outpatient visits (24 and 48 hours following the inpatient visit). The first inpatient visit will be to determine the single-dose pharmacokinetics in the Siliphos naive patient. The second will be to document steady state dynamics following one week on a regular dose of Siliphos at 160 mg po bid. Two to four weeks will elapse between the two tests. The pharmacokinetic test will include blood and urine collection during a 25 hour inpatient stay at the General Clinical Research Center (GCRC) at the Audie L. Murphy VA Hospital (ALMVAH) followed by two outpatient visits 24 and 48 hours after discharge. Blood and urine samples are also taken at the outpatient visits. CLINICAL RELEVANCE: Siliphos is a potent antioxidant that may prevent renal damage, reduce insulin resistance in diabetic patients and correct lipid abnormalities.