NON ANTIMICROBIAL ACTIONS OF CLARITHYROMYCIN (BIAXIN) IN ADULTS WITH ASTHMA

克拉霉素（BIAXIN）对成人哮喘患者的非抗菌作用

• 批准号: 6114212
• 负责人: JOSEPH SPAHN
• 金额: $ 3.22万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6114212
• 关键词: antiinflammatory agents; asthma; clarithromycin; clinical research; dexamethasone; drug interactions; human subject; lymphocyte proliferation; methylprednisolone; pharmacokinetics; steroid metabolism

Macrolide antibiotics such as troleandomycin (TAO) have been used in the treatment of severe asthma. Clarithromycin (Clar), a new macrolide antibiotic, is being used with increasing frequency in patients with poorly controlled asthma. We thus sought to determine whether Clar displays anti-inflammatory effects by measuring its ability to suppress PHA-induced lymphocyte proliferation (LP). Peripheral blood mononuclear cells from 5 asthmatics were co-incubated with PHA (5 mg/mg) & Clar (1,10, and 20mg/ml) in the presence and absence of increasing concentrations of Dexamethasone (Dex). Clar (20 mg/ml) alone resulted in suppression of proliferation, & an additive effect was noted when Clarithromycin was co-incubated with Dex (table; p=ANOVA O vs 20). Since macrolides can alter glucocorticoid metabolism, we also determined the effect of Clarithromycin on methylprednisolone (MPn), Pn 40 mg/1.73 m2) were perfermed prior to & after a 7 d course of Clar. Clar therapy resulted in a 65% reduction in MPn CL (375 8+ vx 130.0 +5ml/min/1.73 m2;p=0.003) while having no effect on Pn CL (238.5+17 vs. 245.0+14 ml/min/1.73 m2). We conclude that Clar causes significant inhibitation of LP alone and amplifies the inhabitation with Dex. In addition, Clarithromycin therapy results in a significant reduction in MPn CL but not PN cl. This delay in MPn, CL, along with the effect on LP may contribute to the beneficial effects of Clar in steroid dependent asthma. In addition, long-term Clar therapy in patients on chronic MPn therapy may increase their risk for steroid-induced adverse effects.

醋竹桃霉素（TAO）等大环内酯类抗生素已用于治疗严重哮喘。克拉霉素（Clar）是一种新的大环内酯类抗生素，在哮喘控制不佳的患者中使用频率越来越高。因此，我们试图通过测量Clar抑制PHA诱导的淋巴细胞增殖（LP）的能力来确定Clar是否显示抗炎作用。将5名哮喘患者的外周血单核细胞与PHA（5 mg/mg）和Clar（1、10和20 mg/ml）在存在和不存在浓度递增的地塞米松（Dex）的情况下共孵育。单独的Clar（20 mg/ml）导致增殖抑制，当克拉霉素与Dex共孵育时注意到累加效应（表; p=ANOVA 0 vs 20）。由于大环内酯类药物可改变糖皮质激素的代谢，我们还测定了克拉霉素对甲基强的松龙（MPn）的影响，在克拉霉素治疗前和治疗7 d后，分别给予40 mg/1.73 m ~ 2的MPn。Clar治疗导致MPn CL降低65%（375 8 ± vx 130.0 ± 5 ml/min/1.73 m2;p=0.003），而对Pn CL无影响（238.5 ± 17 vs. 245.0 ± 14 ml/min/1.73 m2）。我们的结论是，Clar导致单独的LP显著抑制，并放大了与Dex的抑制。此外，克拉霉素治疗可显著降低MPn CL，但不能降低PN CL。MPn、CL、沿着对LP的影响的这种延迟可能有助于Clar在类固醇依赖性哮喘中的有益作用。此外，长期接受MPn治疗的患者长期接受Clar治疗可能会增加类固醇诱导不良反应的风险。