GANCICLOVIR AFTER VALGANCICLOVIR, GANCICLOVIR IN LIVER TRANSPLANT

需要免疫抑制药物来防止器官移植后的移植物排斥反应。 这些药物的主要副作用是增加感染率。 其中一种主要的感染是巨细胞病毒（CMV），其可导致肝炎、胃炎、肺炎和死亡。 这种感染是治疗和预防更昔洛韦。 在部分由印第安纳州大学进行的研究中，更昔洛韦的口服制剂被证明可以预防肝脏患者的CMV感染。 虽然有效，但只有约8%的剂量被吸收，需要高剂量的更昔洛韦。 此外，虽然血液中获得的水平足以预防CMV，但不足以治疗感染。 已开发出更昔洛韦的一种新衍生物，即缬更昔洛韦，在对艾滋病毒患者的初步研究中，发现其达到相当于静脉注射更昔洛韦的水平，剂量小于口服更昔洛韦。 如果这些结果在移植患者中成立，那么需要更少的药丸来预防CMV，提高依从性，并且CMV可以用口服而不是静脉注射药物治疗，从而降低成本。本研究的主要目的是确定肝移植受者每日一次给予缬更昔洛韦的剂量，该剂量提供的更昔洛韦暴露量介于静脉注射5 mg/kg/天更昔洛韦和口服3000 mg/天更昔洛韦之间。 这将通过使用开放标签随机化4向交叉研究测量GCRC中的更昔洛韦药物来评估。 预计将在5家机构对24名患者进行研究。

Immunosuppressive medications are required to prevent graft rejection after organ transplantation. A major side effect of these drugs is an increased rate of infections. One of the major infections is cytomegalovirus (CMV) which can lead to hepatitis, gastritis, pneumonitis, and death. This infection is both treated and prevented with ganciclovir. In studies conducted partially at Indiana University, an oral formulation of ganciclovir was shown prevent CMV infection in liver patients. Although effective, only about 8% of the dose is absorbed necessitating high doses of the ganciclovir. In addition, although the levels obtained in the blood are adequate to prevent CMV they are not adequate to treat infection. A new derivative of ganciclovir, valganciclovir, has been developed that in preliminary studies in patients with HIV, has been found to achieve levels equivalent to intravenous ganciclovir with a smaller dose than the oral ganciclovir. If these results hold true in transplant patients, then fewer pills would be needed to prevent CMV, improving compliance, and CMV could be treated with an oral rather then intravenous drug, thereby reducing cost. The primary purpose of this study is to determine a dose of valganciclovir given once daily to liver transplant recipients that provides a ganciclovir exposure between that provided by intravenous ganciclovir given at 5 mg/kg/day and that provided by oral ganciclovir given at 3000 mg/day. This will be assessed by measuring ganciclovir phamacokinetics in the GCRC using an open label randomized 4-way crossover study. It is anticipated that 24 patients will be studied at 5 institutions.