Steady-state pharmacokinetics and sputum penetration of lomefloxacin in patients with chronic obstructive pulmonary disease and acute respiratory tract infections

Oral doses of 400 mg of lomefloxacin were administered once daily prior to breakfast to 10 middle-aged to elderly hospitalized patients with chronic obstructive pulmonary disease during treatment for bronchopulmonary infections. Serial plasma and sputum samples and fractional urine samples were obtained over a steady-state dosing interval. Lomefloxacin concentrations were determined in duplicate by a validated agar well diffusion microbiological assay. The maximum plasma lomefloxacin concentration (4.5 ± 1.8 mg/liter), the time of occurrence of the maximum concentration (1.7 ± 1.6 h), and the apparent volume of distribution associated with the terminal phase (2.19 ± 1.05 liter/kg) were comparable to the values reported for healthy, young volunteers. Compared with the data reported for young adults, the elimination half-life (12.7 ± 4.67 h) was longer and the apparent total body clearance (132 ± 36.6 ml/min/1.73 m²) was lower in middle-aged to elderly patients. These differences were most likely attributable to age-related decreases in renal function, as evidenced by the lower lomefloxacin renal clearance (70.3 ± 33.5 ml/min) in patients. The presence of acute respiratory infection per se did not appear to alter lomefloxacin pharmacokinetics. The peak lomefloxacin concentration in purulent, expectorated sputum samples of 4.3 ± 1.2 mg/liter occurred 3.1 ± 1.7 h after dose administration and subsequently declined to 1.7 ± 0.5 mg/liter at the end of the 24-h dosing interval. The percent penetration into sputum, as assessed by comparing the area under the curve for sputum and plasma samples, was 120 ± 39.8 (range, 70 to 185). The steady-state lomefloxacin concentrations in plasma and sputum samples from ill, older patients were in excess of the MICs for 90% of the strains tested of common, susceptible respiratory pathogens over most of the dosing interval.