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

大环内酯类抗生素，如曲安霉素(TAO)，已用于治疗 治疗严重哮喘。克拉霉素(Clar)，一种新的大环内酯 抗生素，正在以越来越高的频率使用于 哮喘控制不佳。因此，我们试图确定Clar是否 通过测量其抑制炎症的能力显示抗炎作用 PHA诱导淋巴细胞增殖(LP)。外周血单核细胞 5例哮喘患者的细胞与PHA(5 mg/ml)和CLAR(1， 10毫克/毫升和20毫克/毫升) 地塞米松(Dex)。CLAR(20 mg/ml)单独作用可抑制 增殖&当与CLAR共同孵育时，注意到了相加效应 用Dex(表；p=ANOVA 0vs 20)。因为大环内酯类可以改变 糖皮质激素代谢，我们还测定了CLAR对 甲基强的松龙(MPN)和强的松龙(PN)清除(CL)。12小时 药代动力学研究(MPN，PN 40 mg/1.73m2)在& 经过7d疗程的治疗。CLAR疗法导致减少65%的 MPN CL(375.8+/-36vs 130.0+/-5ml/min/1.73m2；p=0.003) 对PNCL的影响(238.5+/-17vs.245.0+/-14ml/min/1.73m2)。我们得出结论 CLAR单独引起对LP的显著抑制，并放大 地塞米松的抑制作用。此外，CLAR治疗可显著提高患者的 MPN CL减少，但PN CL不减少。MPN CL中的此延迟，以及 对LP的影响可能与Clar在类固醇中的有益作用有关 依赖型哮喘。此外，长期接受CLAR治疗的患者 慢性MPN治疗可能会增加他们患类固醇不良反应的风险 效果。在任何受试者中都没有严重的不良反应。我们有 未发布与此协议有关的任何内容，因为它当前在 进步。

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/ml) & Clar (1, 10, and 20 mg/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 Clar was co-incubated with Dex (table; p = ANOVA 0 vs 20). Since macrolides can alter glucocorticoid metabolism, we also determined the effect of Clar on methylprednisolone (MPn) & prednisolone (Pn) clearance (CL). 12 hr pharmacokinetic studies (MPn, Pn 40 mg/1.73 m2) were performed prior to & after a 7 d course of Clar. Clar therapy resulted in a 65% reduction in MPn CL (375.8+/-36 vs 130.0+/-5 ml/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 inhibition of LP alone and amplifies the inhibition with Dex. In addition, Clar 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. There were no serious adverse effects in any subject. We have not published anything with regard to this protocol as it is currently in progress.