CLINICAL TRIAL: PI & PHARMACOKINETIC STUDY OF DRUG FOR SOLID TUMORS & LYMPHOMAS

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。 这是一项I期、多中心试验，旨在确定伏立诺他在不同程度肝功能障碍患者中的药代动力学分布。伏立诺他是组蛋白脱乙酰酶（HDAC）的抑制剂，组蛋白脱乙酰酶是催化从蛋白质（包括组蛋白和转录因子）的赖氨酸残基去除乙酰基的酶。 HDAC抑制剂可以在体外诱导肿瘤细胞生长停滞、分化或凋亡，并抑制动物肿瘤生长，最终目标是使用该药物治疗实体瘤，因此肿瘤进展将是本研究的次要目的。伏立诺他最近已被美国FDA批准（400 mg PO QD），用于治疗在两种全身治疗期间或之后患有进行性、持续性或复发性疾病的皮肤T细胞淋巴瘤（CTCL）患者的皮肤表现。伏立诺他的半衰期很短，不到2小时。伏立诺他的主要代谢途径涉及葡萄糖醛酸化，目前尚无关于在肝功能障碍患者中适当使用伏立诺他的数据。

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. This is a Phase 1, multicenter trial to determine the pharmacokinetic disposition of vorinostat is patients with varying degrees of hepatic dysfunction. Vorinostat is an inhibitor of Histone deacetylases (HDAC), enzymes that catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. HDAC inhibitors can induce tumor cell growth arrest, differentiation, or apoptosis in vitro and inhibit tumor growth in animals and the eventual goal is to use this drug to treat solid tumors, and therefore tumor progression will be a secondary aim of the study. Vorinostat has recently been approved by the US FDA (400 mg PO QD) for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat has a short half life of less than 2 hours. The major pathways of metabolism of vorinostat involve glucuronidation and There are no data regarding the appropriate use of vorinostat in patients with hepatic dysfunction.