STAVUDINE INTERACTION WITH AGENTS FOR OPPORTUNISTIC INFECTIONS IN HIV PATIENTS

这项针对HIV感染患者的药物相互作用研究试图 司他夫定(D4T)单独给药时的药代动力学 与三种通常用于管理机会主义的药物相结合 感染。 10名患者(1名女性，9名男性)进入研究：8名高加索人， 1名西班牙裔，1名非裔美国人。注册时的平均CD4计数为 62个细胞/mm~3(范围9-143)。 有2例III级毒性反应：2例患者可能有中性粒细胞减少症 由于他们(甲氧苄氨嘧啶/磺胺甲恶唑)的预防。这些插曲 通过将患者转换为喷雾剂喷雾剂而得以解决。 研究用药的不良反应包括(1)d4T，1例患者 报告的周围神经病变；(2)克拉霉素，4例 报告“味道不好”，3个报告胃肠道症状，我报告 皮疹；(3)利福布汀，1名患者报告皮疹；(4)氟康唑 和更昔洛韦，各有3名患者出现胃肠道症状。 截至1997年1月，只对d4T水平进行了分析。组合 氟康唑、利福布汀、克拉霉素和更昔洛韦 显著改变峰值d4T水平、d4T曲线下面积或时间 至最大d4T级别。这些发现表明，这些药物可以 与D4T安全搭配使用。 相关药物水平的药代动力学研究正在进行中；最终 预计结果将在未来3-4个月内公布。

This drug interaction study in HIV-infected patients sought to characterize the pharmacokinetics of stavudine (D4T) when given alone and in combination with three drugs commonly used to manage opportunistic infections. Ten patients (1 female, 9 males) were enrolled in the study: 8 Caucasians, 1 Hispanic, and 1 African-American. The mean CD4 count at enrollment was 62 cells/mm3 (range 9-143). There were 2 Grade III toxicities: 2 patients had neutropenia, presumably due to their (trimethoprim/sulfamethoxazole) prophylaxis. These episodes were resolved by switching the patients to aerosolized pentamidine. Adverse effects by study medication included (1) for D4T, 1 patient reported peripheral neuropathy; (2) for clarithromycin, 4 patients reported "bad taste," 3 reported gastrointestinal symptoms, and I reported rash; (3) for rifabutin, 1 patient reported rash; and (4) for fluconazole and ganciclovir, 3 patients each reported gastrointestinal symptoms. As of January 1997, only the D4T levels have been analyzed. Combinations of fluconazole, rifabutine, clarithromycin, and ganciclovir did not significantly alter the peak D4T level, D4T area under the curve, or time to maximum D4T level. These findings suggest that these drugs can be safely used in combination with D4T. Pharmacokinetic studies of the concomitant drug levels are ongoing; final results are expected in the next 3-4 months.