Taki Hisashi, Ogawa Kenji, Nakagawa Taku, Kashima Kaori, Tarumi Osamu, Saitou Yuko, Yamada Noritaka, Tano Masao, Nikai Toshiaki
Department of Pharmacy, NHO Higashi Nagoya National Hospital, 5-101, Umemorizaka, Meito-ku, Nagoya-shi, Aichi 465-8620, Japan.
Kekkaku. 2007 Aug;82(8):641-6.
We reviewed the interaction between rifampicin (RFP) and clarithromycin (CAM) during treatment of pulmonary Mycobacterium avium complex infection.
The subjects were patients with pulmonary non-tuberculous acid-fast bacillus infection during the period from September 2004 to January 2006 who consented to this study. Drug blood concentrations were compared with the minimum inhibitory concentrations for M. avium isolated from sputum and blood levels of CAM were assessed when the time of administration was changed for RFP.
The blood concentration of CAM showed a marked decrease in all cases (n = 6) when administered together with RFP, but there was no significant difference in the blood concentration of 14-R-hydroxy-clarithromycin (M-5), the active metabolite of CAM. However, the total blood concentration of CAM and M-5 showed a significant fall, similar to the blood concentration of CAM alone. When the blood concentration and bacterial MIC were compared for RFP, the blood concentration exceeded five MIC(s) in six samples as did the CAM+M-5 level in four out of six samples. There was no significant difference in the blood concentration of CAM (n = 5) when the time of RFP administration was altered. CONCLUSION; Because the total blood concentration of CAM+M-5 fell markedly by co-administration of RFP, this might have an influence on the antibacterial effect of CAM. In addition, examination of the administration of RFP and CAM at different times showed that the blood concentration of CAM did not increase and the influence of induction of hepatic drug-metabolizing enzymes by RFP could not be avoided.
我们回顾了利福平(RFP)与克拉霉素(CAM)在治疗肺部鸟分枝杆菌复合群感染期间的相互作用。
研究对象为2004年9月至2006年1月期间同意参与本研究的肺部非结核分枝杆菌感染患者。将药物血药浓度与从痰液中分离出的鸟分枝杆菌的最低抑菌浓度进行比较,并在改变RFP给药时间时评估CAM的血药水平。
当与RFP联合给药时,所有病例(n = 6)的CAM血药浓度均显著下降,但CAM的活性代谢产物14 - R - 羟基克拉霉素(M - 5)的血药浓度无显著差异。然而,CAM和M - 5的总血药浓度显著下降,与单独使用CAM时的血药浓度相似。比较RFP的血药浓度和细菌MIC时,六个样本中有六个样本的血药浓度超过五个MIC,六个样本中有四个样本的CAM + M - 5水平也是如此。改变RFP给药时间时,CAM的血药浓度(n = 5)无显著差异。结论:由于联合使用RFP时CAM + M - 5的总血药浓度显著下降,这可能会影响CAM的抗菌效果。此外,对不同时间给予RFP和CAM的研究表明,CAM的血药浓度并未升高,且无法避免RFP对肝药代谢酶的诱导作用。