Clinical analysis of drug interaction between rifampicin and clarithromycin which are used for treating pulmonary Mycobacterium avium complex infection

Abstract

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.