Pulmonary Disposition of Lomefloxacin in Patients ...

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process 21. Ciprofloxacin displays relatively low penetration into the ELF 22; for other fluoro- quinolones (sparfloxacin 22, temafloxacin 23 and pefloxacin 24) ...
REPRINT Journal of Chemotherapy

Vol. 13 - n. 4 (407-412) - 2001

REVIEW

Pulmonary Disposition of Lomefloxacin in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. A Multiple-Dose Study M. CAZZOLA 1 - M.G. MATERA 2 - M.A. TUFANO 3 - P. CATALANOTTI 3 M. POLVERINO 4 - V. CANTONI 5 - F. FICI 5 - F. SARLO 5 - F. ROSSI 2 1 Divisione di Pneumologia ed Allergologia e Settore di Farmacologia Clinica Respiratoria, A.O.R.N. “A. Cardarelli”, Napoli, 2 Sezione di Farmacologia, and 3 Sezione di Microbiologia e Microbiologia Clinica, Dipartimento di Medicina Sperimentale, Seconda Università di Napoli, 4 Servizio di Fisiopatologia Respiratoria, Ospedale S. Maria dell’Olmo, Cava dei Tirreni, 5 Direzione Medica, Lusofarmaco, Milano, Italy.

Correspondence: Mario Cazzola, M.D., Via del Parco Margherita 24, 80121 Napoli, Italy - Email: [email protected]

Summary In this study we have measured the concentrations of lomefloxacin at steady state in serum and in the intrapulmonary region at specified intervals for 24 h following administration of the last dose of drug in patients suffering from acute exacerbation of chronic obstructive pulmonary disease (COPD). Twenty subjects were enrolled. They received lomefloxacin 400 mg orally once-daily for 5 consecutive days. All patients were divided into five groups, with 4 subjects in each group, according to sampling times (2, 4, 8, 12, and 24 h after the last dose). At bronchoscopy, bronchial biopsies and bronchoalveolar lavage (BAL) were performed. At 12 h after the last dose, serum concentration of lomefloxacin was >1.0 µg/mL and at 24 h it was still detectable, but, at all times, the concentrations in bronchial secretion, bronchial mucosa, and epithelial lining fluid (ELF) were greater than the concentrations in serum [bronchial secretions (µg/mL) = 2.5 ± 1.2; 2.2 ± 1.0: 2.0 ±1.1; 1.8 ± 1.1; 0.6 ± 0.3. bronchial mucosa (µg/g) = 5.9 ± 2.1; 6.2 ± 1.8; 2.6 ± 2.2; 1.9 ± 1.5; 1.0 ± 0.9. ELF (µg/mL) = 6.9 ± 2.8; 5.9 ± 2.6; 3.1 ± 1.9; 2.2 ± 1.0; 0.8 ± 1.3. serum (µg/mL) = 3.2 ± 1.4; 2.8 ± 0.9: 2.1 ± 1.5; 1.2 ± 1.1; 0.4 ± 0.8]. We must stress that we observed a large inter-individual variability in concentrations. Our data show that lomefloxacin once-daily induces high and sustained concentrations in the various potential sites of pulmonary infection and clearly indicate that the pharmacokinetic behavior of this fluoroquinolone permits once-daily administration in patients with acute exacerbations of COPD.

Key words: Lomefloxacin, pulmonary penetration, acute exacerbations of chronic bronchitis, quinolone, difluoroquinolone.

© E.I.F.T. srl - Firenze

ISSN 1120-009X

408

M. CAZZOLA

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M.G. MATERA

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M.A. TUFANO

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CATALANOTTI

INTRODUCTION

Lomefloxacin is a difluoroquinolone with in vitro activity comparable to that of the other quinolones 1. Its pharmacokinetic characteristics, including high serum and tissue concentrations and long half-life (7-8 h), after oral administration, allow once-daily dosing 2. After a single oral dose, lomefloxacin is rapidly absorbed and reaches adequate bactericidal concentrations in most tissues and fluids, including bronchial mucosa 3 and bronchial secretions 4. Both bronchial sites, mucosa and lumen (secretions), are important since they are involved in acute bacterial bronchopulmonary infections induced by Haemophilus influenzae, streptococci and Moraxella catarrhalis 5 . Therefore, the effective pulmonary penetration of lomefloxacin makes this fluoroquinolone a suitable candidate in the treatment of acute exacerbations of chronic bronchitis. After multiple oral administrations, no correlation was observed between sampling time (up to 7 h after the last dose) and lomefloxacin concentration in bronchial mucosa, indicating that steady-state concentrations had been achieved 3. However, Bergogne Bérézin et al. 4 found that, whereas the serum concentrations were stable as a function of time (up to 4 h after the last dose), the mean concentrations in bronchial secretions increased. The purpose of the study was to measure the concentrations of this fluoroquinolone at steady state in serum and in the intrapulmonary region and at specified intervals for 24 h following administration of the last dose of drug in patients suffering from acute exacerbation of chronic obstructive pulmonary disease (COPD).

PATIENTS AND METHODS

In total 20 patients suffering from acute exacerbation of chronic bronchitis were enrolled in this open-label study. Ethics Committee approval of the study was obtained and all patients provided informed consent. The diagnosis of COPD was consistent with the diagnostic standards of the consensus statement of the European Respiratory Society 6 and established on the basis of clinical history, physical findings, spirometry (FEV1 >70% predicted

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M. POLVERINO

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CANTONI

- F.

FICI

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SARLO

- F.

ROSSI

in the presence of obstruction assessed as FEV1/VC