EFFECT OF RITONAVIR ON THE PHARMACOKINETICS OF MEPERIDINE IN HIV NEGATIVE SUBJECT

利托那韦对HIV阴性受试者哌替啶药代动力学的影响

• 批准号: 6163407
• 负责人: S PISCITELLI
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6163407
• 关键词: HIV infections; clinical research; combination chemotherapy; drug adverse effect; drug screening /evaluation; human subject; meperidine; pharmacokinetics; protease inhibitor

Human immunodeficiency virus (HIV)-infected patients may require administration of meperidine for pain control or chills and rigors associated with interleukin-2 or amphotericin B. Ritonavir (Norvir) is a protease inhibitor that is a potent inhibitor of cytochrome P-450, the major enzyme system involved in drug metabolism. The combination of ritonavir and meperidine could theoretically lead to increased meperidine concentrations and toxicity, and thus, their concomitant administration is contraindicated. This study will characterize the pharmacokinetics of meperidine and its major metabolite, nor-meperidine, in eight HIV-negative, healthy patients. Subjects will receive a 50 mg dose of PO meperidine on day 0 of the study. Serial samples will be drawn over 48 hours for determination of meperidine and nor-meperidine concentrations. Ritonavir will be initiated on day 2 and escalated to a dose of 500 mg BID over 5 days. After a total of 10 days of ritonavir, a 50 mg PO dose of meperidine will again be administered and samples will be collected over 72 hours while continuing ritonavir through the sampling period. Maximum blood level, time to maximum blood level, area under the curve, and clearance will be compared between the two groups. The study will provide data on meperidine disposition in patients receiving concomitant ritonavir. Currently, subject enrollment and study has been completed and data are being analyzed.

人类免疫缺陷病毒（艾滋病毒）感染者 患者可能需要给予哌替啶以控制疼痛 或与白细胞介素-2或白细胞介素B相关的寒战和寒战。 利托那韦（Norvir）是一种蛋白酶抑制剂，是一种强效的 细胞色素P-450是参与药物代谢的主要酶系统， 新陈代谢.利托那韦和哌替啶的组合可以 理论上导致哌替啶浓度增加， 毒性，因此，它们的伴随施用是 禁忌。本研究将描述药代动力学 八个国家的度冷丁及其主要代谢产物去甲度冷丁含量 HIV阴性的健康病人受试者将接受50 mg剂量 在研究的第0天PO哌替啶。系列样品将 在48小时内抽取样品，用于测定哌替啶， 去甲哌替啶浓度。利托那韦将在第2天开始给药 并在5天内递增至500 mg BID的剂量。共经过 利托那韦10天后，将再次口服50 mg哌替啶 将在72小时内给药并采集样本， 在整个采样期间持续利托那韦。最大血液 水平、达到最大血药浓度的时间、曲线下面积，以及 将比较两组之间的清除率。这项研究将 提供接受哌替啶治疗的患者中哌替啶分布的数据 伴随利托那韦。目前，受试者入组和研究已 已完成，数据正在分析中。