The Effect of Multiple-Dose Oral Lomefloxacin on Theophylline Metabolism in Man

Abstract

Single-dose plasma pharmacokinetics of theophylline (6 mg/kg intravenously) and renal excretion of theophylline and its metabolites, resulting from 8-oxidation and N-demethylation, were investigated in eight healthy volunteers before and at day 3 of concomitant oral administration of the quinolone derivative lomefloxacin (400 mg twice daily). Plasma samples were collected until 24.5 h, and urine samples were collected until 72 h after theophylline administration. The concentrations of theophylline and the major metabolites, resulting from N-demethylation and 8-oxidation, were measured utilizing a high-pressure liquid chromatography (HPLC) technique. No significant changes in theophylline half-life, volume of distribution, protein binding, total body clearance, or renal clearance were noted. In addition, renal excretion of unchanged theophylline, the products of the N-demethylation, 3-methylxanthine, and 1-methyluric acid, and the product of the 8-oxidation, 1,3-dimethyluric acid, were not altered by simultaneous administration of lomefloxacin. Orally administered lomefloxacin is absorbed quickly and to a high extent. During administration of 400 mg twice daily, plasma concentrations reached are well above minimum inhibitory concentration (MIC) values of pathogens that are frequently isolated in lower respiratory tract infections. This study shows that lomefloxacin in a twice daily dose of 400 mg does not effect theophylline metabolism. Lomefloxacin and theophylline can be coadministered without concern about effects of lomefloxacin on theophylline pharmacokinetics.