Penetration of Ciprofloxacin and Metabolites into Human Lung, Bronchial and Pleural Tissue after 250 and 500 mg Oral Ciprofloxacin

Abstract

Ciprofloxacin (CIP) and metabolite concentrations in lung tissue, parietal pleura and bronchial tissue were assessed in 43 adult patients who underwent lung surgery. A single oral dose of CIP was given for prophylaxis of bacterial infections. Two to 6 h prior to tissues sampling, 23 patients received 250 mg and 20 subjects 500 mg of the substance. Blood plasma samples were obtained at the same time as the lung tissue samples. CIP and its metabolites were assayed chemically by high-pressure liquid chromatography (HPLC). After 250 mg CIP, the individual lung tissue CIP concentrations during the 2- to 6-hour post-dose period ranged from 0.5 to 4.8 mg/kg. In 20 of the 23 lung samples, the CIP concentrations were above 1 mg/kg. After 500 mg CIP, the corresponding lung CIP concentrations ranged from 1.6 to 6.0 mg/kg. The CIP lung concentrations were, irrespective of the dose size, between 2 and 7 times higher than the simultaneous blood plasma concentrations. This indicates an excellent penetration of CIP and its metabolites into lung tissue. Bronchial tissue was obtained in 9 cases. Penetration into bronchial mucosa tissue was good as well, as indicated by tissue/plasma ratio values between 1.5 and 4.4. Individual CIP concentrations in the patients given 250 mg CIP, ranged from 1.0 to 1.6 mg/kg. In the patients who received 500 mg, the range was from 1.7 to 3.4 mg/kg. Tissue/plasma ratio values between 0.8 and 2.1 indicated that penetration to pleural tissues was good as well. Metabolite concentrations in all of the tissues assayed (lung, bronchial mucosa, pleural tissue) were low when compared to the concentrations of CIP. The concentrations in lung, pleural and bronchial tissue will probably permit low doses in the treatment of most respiratory tract infections. The broad spectrum of antibacterial activity, the good tissue penetration, chemical stability and the good safety record of the substance means that the drug is potentially a useful agent for perioperative antibiotic prophylaxis.

Transepithelial transport of the fluoroquinolone ciprofloxacin by human airway epithelial Calu-3 cells

“…Levels of ciprofloxacin in pleural fluid, sputum, bronchial secretions, and saliva are similar and comparable to levels in serum after 12-h periods (3). Metabolite concentrations in all tissues assayed (lung, bronchial mucosa, and pleural tissue) are low compared to ciprofloxacin concentrations (20). The fluoroquinolone ofloxacin also penetrates well into human lung tissue (22), as do enoxacin (25) and lomefloxacin (2).…”

“…Pharmacokinetic studies demonstrate that ciprofloxacin and other fluoroquinolones penetrate well into fluids and tissue of the lung. Ciprofloxacin concentrates well into lung tissue (20). Levels of ciprofloxacin in pleural fluid, sputum, bronchial secretions, and saliva are similar and comparable to levels in serum after 12-h periods (3).…”

Ciprofloxacin is a potential topoisomerase II inhibitor for the treatment of NSCLC

“…Drug dose after an oral administration reaches 4.3 μ g/ml concentration in the serum. The concentration of ciprofloxacin after an oral administration is up to 7 times higher in the lung tissue than in the serum (20). This indicates that the maximum concentration of ciprofloxacin after an oral dose of one 750 mg tablet can reach 30.1 μ g/ml.…”

Assessment of antibiotic levels in lung tissue with erosion-controlled dosage forms

“…The pharmacokinetic parameters of various fluoroquinolones have been established in a mouse model of infected lung (6), and it was determined that infection did not affect the tissue distribution of these drugs. The aim of other studies was to evaluate the penetration of ciprofloxacin in the bronchial tissue (7,8) and, more specifically, in the bronchial mucosa (9,12) or in the pleural fluid (13). Transcapillary exchange of antibiotics is carried out by diffusion and occurs in the capillary beds of the tissues.…”