MMWR Morb Mortal Wkly Rep. 1996 Oct 25;45(42):921-5.
In 1995 and 1996, the Food and Drug Administration (FDA) approved three products in the new protease inhibitor class of drugs--saquinavir (Invirase), ritonavir (Norvir), and indinavir (Crixivan). Another drug in this class of agents, nelfinavir (Viracept) (Agouron Pharmaceuticals), is expected to be available soon from the manufacturer through an expanded-access program. All four drugs, which inhibit HIV protease and thus interfere with viral maturation and replication, are the most potent antiretroviral agents available to treat patients with HIV disease. However, these protease inhibitors interact with rifamycin derivatives, such as rifampin and rifabutin, which are used to treat and prevent the mycobacterial infections commonly observed in HIV-infected patients. Rifamycins accelerate the metabolism of protease inhibitors (through induction of hepatic P450 cytochrome oxidases), resulting in subtherapeutic levels of the protease inhibitors. In addition, protease inhibitors retard the metabolism of rifamycins, resulting in increased serum levels of rifamycins and the likelihood of increased drug toxicity. This report describes approaches for managing patients who are candidates for or who are undergoing protease inhibitor therapy when tuberculosis (TB) is diagnosed and presents interim recommendations for managing these patients until additional data are available and formal guidelines are issued.
1995年和1996年，美国食品药品监督管理局（FDA）批准了新型蛋白酶抑制剂类药物中的三种产品——沙奎那韦（英地那韦）、利托那韦（诺维拉平）和茚地那韦（克力芝）。该类药物中的另一种药物奈非那韦（维乐命）（阿古伦制药公司）预计制造商将很快通过扩大使用计划提供。所有这四种药物都能抑制HIV蛋白酶，从而干扰病毒成熟和复制，是治疗HIV疾病患者可用的最有效的抗逆转录病毒药物。然而，这些蛋白酶抑制剂与利福霉素衍生物相互作用，如利福平、利福布汀，它们用于治疗和预防HIV感染患者中常见的分枝杆菌感染。利福霉素会加速蛋白酶抑制剂的代谢（通过诱导肝P450细胞色素氧化酶），导致蛋白酶抑制剂水平低于治疗剂量。此外，蛋白酶抑制剂会延缓利福霉素的代谢，导致利福霉素血清水平升高和药物毒性增加的可能性。本报告描述了在诊断出结核病（TB）时，对适合或正在接受蛋白酶抑制剂治疗的患者进行管理的方法，并提出了在获得更多数据和发布正式指南之前管理这些患者的临时建议。
