Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or rifabutin for Mycobacterium avium-M. intracellulare infection.

Abstract

The newer macrolides and rifamycins (rifabutin) are major advances for treatment or prophylaxis of disease due to Mycobacterium avium complex. Although rifampin and rifabutin are known to induce the hepatic cytochrome P-450 system, their impact on the metabolism of clarithromycin is unknown. Clarithromycin and its major metabolite, 14-OH clarithromycin, were measured in the sera of patients receiving 500 mg twice a day before and after the addition of antituberculous drugs, including 600 mg/day of rifampin or rifabutin. Mean serum levels of clarithromycin given as a single agent were 5.4 +/- 2.1 micrograms/mL. These decreased to 0.7 +/- 0.6 micrograms/mL in patients receiving rifampin and 2.0 +/- 1.5 micrograms/mL in those receiving rifabutin. Mean serum levels of 14-OH clarithromycin were similar in the 3 groups (1.8-1.9 micrograms/mL). Rifampin and (to a lesser degree) rifabutin appear to induce the metabolism of clarithromycin.