A microdialysis study of pharmacokinetics of orally or intravenously administrated levofloxacin in lung tissues of the Streptococcus pneumoniae pneumonia rat

Objective: To characterize the pharmacokinetics (PK) of differently administered levofloxacin drug in the lung tissues of rats Streptococcus pneumoniae pneumonia. Methods: The rat model of pneumococcal pneumonia was established. Levofloxacin was administered through oral or intravenous route such that it simulated the 400 mg/d dose in patients. Microdialysis technique was used to collect the blood and lung samples simultaneously from rats with pneumonia infection. Microdialysis technique also helped to characterize the changes in the concentration of free levofloxacin. Results: 1.20 minutes after intravenous administration, the concentration of levofloxacin reached its peak value (C-max) (28.08 +/- 9.88) mu g/mL in lungs: the peak concentration was approximately equal to the concentration in blood. Then, the concentration decreased simultaneously in both lungs and blood. The penetrate rate (PR) of levofloxacin in lungs is 1.0111 +/- 0.21. Elimination half-life (t(1/2)) is (229.9 +/- 55.6) min in blood and (232.8 +/- 74.2) min in lungs. The Area Under Curve (AUC((0-inf))) values of drug-time curves are (4167.6 +/- 1721.6) mu g.min/mL in blood and (3372.7 +/- 1086.4) mu g.min/mL in lungs, respectively. The distribution coefficient (AUC lung /AUC blood) is (1.0394 +/- 0.85). 2. After oral administration, there were similar trends of increase and decrease in free levofloxacin concentration of blood and lungs. After 20 minutes, the average concentration in the lung tissue tends to be higher than that in the blood. The PR of levofloxacin in lungs is (1.1678 +/- 0.06). The free form of levofloxacin concentration C-max is (1.29 +/- 0.41) mu g/mL in blood and (1.56 +/- 0.7) mu g/mL in lungs. The t(1/2) is (534.4 +/- 381.6) minutes in blood and (591.4 +/- 416.1) minutes in lungs. The AUC((0-inf)) is (920.3 +/- 473.6) min.mu g/mL in blood and (1196.2 +/- 992.4) min.mu g/mL in lungs, respectively. The AUC(lung)/AUC(blood) is (1.2188 +/- 0.56). 3. Comparing between groups, the C-max and AUC in both blood and lungs are significantly lower in case of oral administration. In contrast, compared with the intravenous administration, the PR in lungs is higher (P < 0.05) when the drug is administered orally to the subjects. Conclusion: At the 400 mg/d dose, levofloxacin concentration reached the peak faster when it was administered through intravenous injection. In this case, the free drug concentration was also found to be higher in blood and lungs of rats with pneumonia. But, the drug concentration continues to be within the mutant selection window, which would potentially lead to the emergence of drug-resistant mutant bacteria. When delivered orally, the C-max and AUC are lower in blood and lungs; therefore, the levofloxacin antibiotic may not kill the bacteria effectively. The application of microdialysis technique in the lung tissue is safe and reliable. Moreover, the microdialysis technique can accurately characterize the pharmacokinetics of drugs in tissues. The technique of microdialysis is demarcated with higher objectivity.