Moxifloxacin in Chronic Obstructive Pulmonary Disease: Pharmacokinetics and Penetration into Bronchial Secretions in Ward and Intensive Care Unit Patients.

This study aimed to evaluate the pharmacokinetic profile of moxifloxacin (MXF) in serum and sputum/bronchial secretions of 22 patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalized in the ward and intensive care unit (ICU). The data showed that ICU patients had lower concentrations in secretions (P = 0.01). However, no other statistically significant differences were observed in pharmacokinetic parameters and penetration in secretions between ward and ICU patients. MXF showed a favorable pharmacokinetic profile, and the pharmacodynamic targets for common pathogens for AECOPD were achieved.

Moxifloxacin pharmacokinetics and pleural fluid penetration in patients with pleural effusion.

The aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24 in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23±1.31 mg/liter, and it was detected 7.50±2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPF was 2.96±1.45 mg/liter, but it was observed significantly earlier, at 3.58±1.38 h (P<0.001). Both groups revealed similar values of AUC24PF (31.83±23.52 versus 32.81±12.66 mg·h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11±0.74 versus 1.17±0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.

Pharmacokinetics of moxifloxacin and high-dose levofloxacin in severe lower respiratory tract infections.

This study evaluated the pharmacokinetics of intravenous moxifloxacin 400 mg once and levofloxacin 500 mg twice daily in patients with lower respiratory tract infections (LRTIs) and assessed their pharmacodynamic adequacy against common respiratory pathogens. Eighteen patients with LRTIs hospitalised in general wards were included. Serial blood samples were obtained at steady state and concentrations were determined using HPLC. Pharmacokinetic variables were estimated by a two-compartment model. The characteristic pharmacodynamic parameter for fluoroquinolones (AUC(0-24)/MIC) was calculated. Peak and trough concentrations were, respectively, 4.81 ± 1.03 and 0.59 ± 1.13 mg/L for moxifloxacin and 6.42 ± 1.08 and 0.79 ± 0.39 mg/L for levofloxacin. Pharmacokinetic data for moxifloxacin and levofloxacin, respectively, were: CL, 10.27 ± 1.24 and 22.66 ± 6.62 L/h; t1/2, 13.43 ± 5.12 and 6.75 ± 1.34 h; Vss, 163.03 ± 53.88 and 170.73 ± 39.59 L; and AUC(0-24), 39.38 ±5.28 and 47.06 ± 14.09 mg·h/L. The pharmacodynamic target was attained in all patients by both antibiotics against the majority of respiratory pathogens. Moxifloxacin proved to be pharmacodynamically efficacious against Gram-positive bacteria with MICs ≤ 0.79 mg/L and Gram-negative bacteria with MICs ≤ 0.32 mg/L. These MIC thresholds for levofloxacin were 1.1 mg/L and 0.38 mg/L, respectively. Moxifloxacin and high-dose levofloxacin show a favourable pharmacokinetic profile in plasma of patients with severe LRTIs, without significant interpatient variability. They ensure optimal pharmacodynamic exposure against the majority of microbes involved in these infections. However, the predicted efficacy against Gram-negative bacteria with MICs ≥ 0.5 mg/L appears to be low.

Saliva and blood concentration of cefuroxime in patients undergoing maxillofacial surgery.

PURPOSE: To investigate the penetration of cefuroxime into the parotid saliva after short-term intravenous administration in patients undergoing various maxillofacial surgical procedures. PATIENTS AND METHODS: A total of 12 patients, 10 males and 2 females, with a mean age of 41 ± 21.2 years, participated in the present study. Each patient received 1.5 g of intravenous cefuroxime every 8 hours. Blood and parotid saliva samples were collected concomitantly, on the third day of therapy, just before the infusion of the first morning dose, and 0.5 hour after its end. All samples were analyzed using high-performance liquid chromatography. RESULTS: The cefuroxime concentration in plasma and saliva before infusion was 2.08 ± 1.05 mg/L and 0.46 ± 0.33 mg/L, respectively. At 30 minutes after the end of infusion, the corresponding concentrations were 55.54 ± 20.24 mg/L and 14.50 ± 7.85 mg/L. The saliva/plasma ratio was 0.25 ± 0.18 before and 0.26 ± 0.12 after the infusion. CONCLUSIONS: Cefuroxime is excreted in saliva in high levels shortly after infusion but is detected in far lower levels 8 hours after infusion. Taking into consideration the minimum inhibitory concentration values of common pathogens, we have concluded that the saliva concentrations of the drug are sufficient against some, but not all, pathogens involved in the oral-maxillofacial area.

Pharmacokinetics of ciprofloxacin and its penetration into bronchial secretions of mechanically ventilated patients with chronic obstructive pulmonary disease.

We evaluated the pharmacokinetic profile of ciprofloxacin and its penetration into bronchial secretions of critically ill patients with chronic obstructive pulmonary disease (COPD). Twenty-five mechanically ventilated patients with severe COPD who were suffering from an acute, infectious exacerbation were included in this prospective, open-label study. All subjects received a 1-hour intravenous infusion of 400 mg ciprofloxacin every 8 h. Serial blood and bronchial secretion samples were obtained at steady state, and concentrations were determined using high-performance liquid chromatography. The pharmacodynamic parameters that are associated with the efficacy of fluoroquinolones against Gram-negative pathogens were also calculated. The mean peak (maximum) concentration (C(max)) and trough (minimum) concentration in plasma were 5.37 ± 1.57 and 1 ± 0.53 mg/liter, respectively. Mean values for volume of distribution, clearance, half-life, and area under the curve from 0 to 24 h (AUC(0-24)) were 169.87 ± 84.11 liters, 26.96 ± 8.86 liters/h, 5.35 ± 2.21 h, and 47.41 ± 17.02 mg · h/liter, respectively. In bronchial secretions, a mean C(max) of 3.08 ± 1.21 mg/liter was achieved in 3.12 ± 1.01 h, and the penetration ratio was 1.16 ± 0.59. The target of AUC(0-24)/MIC of ≥125 was attained in all patients, in the majority of them (76%), and in none at MICs of 0.125, 0.25, and 1 µg/ml, respectively. Slightly better results were obtained for the ratio C(max)/MIC of ≥10. In conclusion, ciprofloxacin demonstrates excellent penetration into bronchial secretions. There is wide interindividual variability in its pharmacokinetic parameters in critically ill COPD patients and inadequate pharmacodynamic exposure against bacteria with MICs of ≥0.5 µg/ml.