Pharmacokinetics and pharmacodynamics of levofloxacin in intensive care patients.

OBJECTIVE: A prospective pharmacokinetic study was performed in Caucasian patients from an intensive care unit with respiratory support to evaluate the influence of this circumstance on the pharmacokinetic behaviour of levofloxacin. PATIENTS AND METHODS: A standard dosage regimen of 500 mg/day was administered to nine Caucasian patients included in the study, irrespective of their demographic characteristics. The experimental data on plasma concentrations were analysed by independent-modelling techniques to estimate the following pharmacokinetic parameters: area under the plasma concentration-time curve (AUC), volume of distribution at steady state (V(ss)), plasma clearance (CL), maximum plasma concentration at steady state (C(max)(,)(ss)) and elimination half-life (t((1/2))(beta)). Multiple regression analysis was applied to establish the type of correlation between the pharmacokinetic parameters and patient characteristics; the Monte Carlo simulation technique was implemented for the pharmacokinetic/pharmacodynamic analysis based on the probability distribution of the values of AUC/minimum inhibitory concentration (MIC) and C(max)(,)(ss)/MIC observed in this group of patients. RESULTS AND CONCLUSION: The results show that for AUC the simplest linear model with creatinine clearance as the only independent variable fits the data at a 99% confidence level, explaining more than 85% of the observed variability in this parameter. The volume of distribution, however, showed a statistical correlation with the severity of the illness (Simplified Acute Physiology Score II), although total bodyweight also explains a high percentage of variability of these parameters. Since the group of patients included in the study was small and also included obese individuals, it is difficult to estimate with precision the contribution of each circumstance (overweight or illness severity) to the pharmacokinetic behaviour of levofloxacin.

Influence of flow rate on the disposition of levofloxacin and netilmicin in the isolated rat lung.

The objective of this study was to examine the influence of the rate at which the tissue is perfused on the disposition of levofloxacin and netilmicin in the pulmonary tissue, using an experimental model of the isolated rat lung. Analysis of the results was performed using two pharmacokinetic approaches. By stochastic analysis of outflow curves the corresponding statistical moments and derived distribution coefficient were calculated. Model-dependent analysis based on a three-compartment dispersion model was also applied to the outflow concentration data. A statistically significant decrease in the distribution coefficient was observed for both antibiotics when the flow rate was decreased. For levofloxacin this parameter takes values of 2.14 and 1.25 mL/g for 10 and 5 mL/min flow rates, respectively. In the case of netilmicin these values were 0.81 and 0.39 mL/g for the higher and lower flow rates, respectively. Model parameters related to the distribution process were also modified as a consequence of the flow rate decrease. Tissue flow rate seems to be a determinant factor on the distribution of levofloxacin and netilmicin in the isolated rat lung.

Cell-based drug-delivery platforms.

Cell systems have recently emerged as biological drug carriers, as an interesting alternative to other systems such as micro- and nano-particles. Different cells, such as carrier erythrocytes, bacterial ghosts and genetically engineered stem and dendritic cells have been used. They provide sustained release and specific delivery of drugs, enzymatic systems and genetic material to certain organs and tissues. Cell systems have potential applications for the treatment of cancer, HIV, intracellular infections, cardiovascular diseases, Parkinson's disease or in gene therapy. Carrier erythrocytes containing enzymes such us L-asparaginase, or drugs such as corticosteroids have been successfully used in humans. Bacterial ghosts have been widely used in the field of vaccines and also with drugs such as doxorubicin. Genetically engineered stem cells have been tested for cancer treatment and dendritic cells for immunotherapeutic vaccines. Although further research and more clinical trials are necessary, cell-based platforms are a promising strategy for drug delivery.