里法皮辛和克林达米辛在葡萄球菌骨关节感染中的药理动力相互作用
T Goulenok1, J Seurat2, A de La Selle3
1Département de Médecine Interne, Hôpital Bichat-Claude Bernard, GHU APHP Nord, Université de Paris, Paris, France.
International journal of antimicrobial agents
|June 11, 2023
概括
利芬素显著降低了稳杆菌骨关节感染 (SOAIs) 中的克林达米辛水平,大大降低了实现治疗目标的可能性. 这种药物相互作用可能导致治疗失败,即使是敏感细菌.
科学领域:
- 药理学 药理学是指药理学的学科.
- 传染性疾病 传染性疾病
- 临床药房 临床药房
背景情况:
- 口服的克林达米辛和利芬素用于稳形菌骨关节感染 (SOAIs).
- 众所周知,里芬素诱导CYP3A4,可能会影响克林达米辛的药理动力学.
- 在SOAIs中这种相互作用的药理动力学/药理动力学 (PK/PD) 后果尚不清楚.
研究的目的:
- 为了量化克林达米辛PK/PD标志物.
- 在SOAI患者中,在Rifampicin同时使用之前和期间评估克林达米辛PK/PD标志物的变化.
- 评估利芬素对克林达米辛暴露和疗效的影响.
主要方法:
- 使用SAEM算法对19名SOAI患者进行了人口药理动力学 (PK) 分析.
- 克林达米辛PK/PD标志物被比较在患者之前和在里芬素同时使用期间 (每个患者作为自己的对照).
- 进行了模拟,以评估使用或不使用利芬辛达到PK/PD目标的概率.
主要成果:
- 利芬素的同时服用增加了克林达胺素清除量的16倍,并减少了AUC0-8h/MIC的15倍 (P < 0.005).
- 在里芬素的服用期间,克林达米辛的平均最低度从2.7 mg/L降至<0.05 mg/L.
- 当利芬素同时使用时,即使对于敏感菌株,达到克林达米辛PK/PD关键标的概率也会显著下降 (例如,%fT>MIC降至1%,AUC0-24h/MIC降至6%).
结论:
- 利芬素的同时使用对SOAI中的克林达米辛暴露和PK/PD目标产生了深远的影响.
- 这种相互作用可能会导致临床失败和潜在的临床失败,即使是敏感的黄金葡萄球菌菌株.
- 临床监测和潜在的剂量调整对于在SOAI治疗中结合克林达米辛和里芬素至关重要.
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