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Effect of Garenoxacin on Eubacteria in the Normal Intestinal Microflora when Administered Concomitantly with Digoxin

Abstract Garenoxacin is a new des-F(6-quinolone with a broad antimicrobial spectrum. It has been reported that antibiotics may raise digoxin concentrations in the plasma of patients who are taking these agents concurrently, possibly due to the effect on the digoxin-metabolizing intestinal microflora. Sixteen healthy subjects were given a loading dose of digoxin (0.25 mg orally, q 6 h) on Day 1 followed by once-daily doses of 0.25 mg on Days 2 through 14. The subjects also received garenoxacin 600 mg orally, q 24 h, on Days 8 through 14. The number of enterococci, bacilli, corynebacteria, enterobacteria, bifidobacteria, lactobacilli, clostridia and bacteroides decreased whereas the number of eubacteria increased in the intestinal microflora. Eubacterium lentum strains increased during the administration of garenoxacin and returned towards normal levels within 14 days after the last dose of garenoxacin. The fecal concentrations of garenoxacin varied between 14.0-310.0 mg/kg. The minimum inhibitory concentrations of garenoxacin against the isolated E. lentum strains were >64 mg/L. There was no degradation of digoxin by the E. lentum strains.