The pharmacokinetics of oral fleroxacin and ciprofloxacin in plasma and sputum during acute and chronic dosing

• Published in: British journal of clinical pharmacology Vol. 49; no. 1; pp. 32 - 38
• Main Authors: Begg, Evan J., Robson, Richard A., Saunders, Darren A., Graham, Garry G., Buttimore, Rona C., Neill, Alister M., Town, G. Ian
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.01.2000; Blackwell Science; Blackwell Science Inc
• Subjects: Adult; Aged; Aged, 80 and over; Anti-Infective Agents - adverse effects; Anti-Infective Agents - blood; Anti-Infective Agents - pharmacokinetics; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Area Under Curve; Biological and medical sciences; Bronchiectasis - metabolism; Bronchitis - metabolism; Chronic Disease; ciprofloxacin; Ciprofloxacin - adverse effects; Ciprofloxacin - blood; Ciprofloxacin - pharmacokinetics; Female; fleroxacin; Fleroxacin - adverse effects; Fleroxacin - blood; Fleroxacin - pharmacokinetics; Humans; Male; Medical sciences; Middle Aged; Models, Biological; Original; pharmacokinetics; Pharmacology. Drug treatments; plasma; sputum; Sputum - metabolism; Time Factors; Fleroxacin; Human; Lung disease; Respiratory disease; Acute; Single dose; Oral administration; Bronchiectasis; Blood plasma; Multiple dose; Infection; Antibiotic; Chemotherapy; Chronic; Fluoroquinolone derivatives; Treatment; Sputum; Bronchus disease; Bronchitis; Obstructive pulmonary disease; Antibacterial agent; Ciprofloxacin; Pharmacokinetics; Quinolone derivatives
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.2000.00105.x

Aims To examine the pharmacokinetics of ciprofloxacin and fleroxacin in plasma and sputum of patients with an acute exacerbation of chronic bronchitis or bronchiectasis following the first dose and again during the third day of treatment. Methods Twelve patients, aged >35 years, with acute infective exacerbation of bronchitis or bronchiectasis were allocated randomly to treatment with either fleroxacin 400 mg daily or ciprofloxacin 500 mg twice daily in an open, parallel group design. Plasma and sputum were collected during the first and third days of treatment. The time course of concentrations in sputum was modelled assuming that it acted as a negligibly small compartment of distribution. Results The mean sputum to plasma ratios of both ciprofloxacin and fleroxacin were approximately 1 on both days 1 and 3. Peak concentrations of ciprofloxacin in sputum were achieved 1.6 (95% CI on mean difference 0.8–2.3) and 1.2 (0.4–1.9) h later than in plasma on day 1 and day 3, respectively (mean difference±95% confidence interval). For fleroxacin, the corresponding delay in time to peak concentrations was less marked and not significant. Fleroxacin accumulated in plasma (accumulation index 1.52±0.07) and sputum (accumulation index 1.79±0.39) from day 1 to day 3. Accumulation did not occur for ciprofloxacin because the dose interval (12 h) was considerable longer than its half life (3–4 h). Conclusions The sputum to plasma ratio of ciprofloxacin and fleroxacin is approximately 1. The time to peak concentrations of ciprofloxacin in sputum is slightly delayed compared with plasma. Fleroxacin accumulates over time in both plasma and sputum consistent with its longer half‐life.