title: Steady-state pharmacokinetics and sputum penetration of lomefloxacin in patients with chronic obstructive pulmonary disease and acute respiratory tract infections.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University Hospital, Utrecht, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: Kovarik
authors.forename: A I
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: J M
authors.initials: JM
authors.lastname: Smit
authors.forename: P A
authors.initials: PA
authors.lastname: Sips
authors.forename: M
authors.initials: M
authors.lastname: Rozenberg-Arska
authors.forename: J H
authors.initials: JH
authors.lastname: Glerum
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D002908:Chronic Disease; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics*; D012141:Respiratory Tract Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D013183:Sputum / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C053091:lomefloxacin