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

人类免疫缺陷病毒(HIV)感染 病人可能需要服用度冷丁来控制疼痛。 或与白介素2或两性霉素B相关的寒战和僵硬。 利托那韦(Norvir)是一种蛋白酶抑制剂，是一种有效的 细胞色素P-450，参与药物作用的主要酶系统 新陈代谢。利托那韦和度冷丁的组合可以 理论上会导致度冷丁浓度升高 毒性，因此，它们的伴随给药是 禁忌。这项研究将描述药物动力学。 度冷丁及其主要代谢物去甲度冷丁在8个月内 HIV阴性、健康的患者。受试者将接受50毫克的剂量 在研究的第0天服用PO度冷丁。序列样本将是 在48小时内抽取，用于测定度冷丁和 去甲度冷丁浓度。利托那韦将在第二天开始使用 并在5天内逐步增加到500 mg，bid。在经历了总共 利托那韦10天，PO剂量50毫克的度冷丁将再次 管理和样本将在72小时内收集，而 在整个抽样期内继续服用利托那韦。最大血量 水平、达到最高血液水平的时间、曲线下面积以及 两组之间的通行证将进行比较。这项研究将 提供有关服用度冷丁的患者的数据 伴随利托那韦。目前，学科招生和学习已 已经完成，数据正在分析中。

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.