Pharmacokinetics of free ertapenem in critically ill septic patients: intermittent versus continuous infusion.

BACKGROUND: The aim of this paper was to compare the pharmacokinetic and pharmacodynamic (PK/PD) parameters of continuous (CI) and intermittent infusion (ITI) of ertapenem into critically ill patients with severe abdominal infections. METHODS: Twenty septic patients hospitalized in a university hospital intensive care unit were enrolled in the study. Half of the patients received ertapenem as an ITI 1 g bolus once daily, and the other half of the patients received the same dose via CI over 24 h following a 1-g loading dose. Blood was drawn 1, 12 and 24 h after terminating ITI or on days 2, 3 and 5 after starting CI for each patient. After centrifugation, the drawn blood was frozen at -80 °C until being examined by high-performance liquid-chromatography analysis. RESULTS: Median serum-free ertapenem concentrations were as follows: ƒCmax = 98.9 mg/L and ƒCmin = 2.5 mg/L for ITI, and ƒCss=15.9 mg/L for CI. The ITI and CI median total clearance and volumes of distribution were 2.2 L/h vs. 2.5 L/h and 15.4 L vs. 21.0 L, respectively. The ertapenem MIC ranges were as follows: Escherichia coli (0.006 to 0.5 mg/L), Enterobacter cloacae (0.023 to 0.5 mg/L), Klebsiella oxytoca (0.023 to 0.5 mg/L), Staphylococcus aureus (0.38 to 3 mg/L), Streptococcus viridians (0.38 to 3 mg/L) and Enterococcus faecalis (0.38 to 3 mg/L). ITI and CI provided steady-state serum-free ertapenem concentrations constantly above the MIC for all bacteria. CONCLUSION: Ertapenem exhibited satisfactory PK/PD parameters and achieved serum-free concentrations 100% of the time, above even the high MIC of extracellular pathogens normally encountered during severe abdominal infections. CI administration resulted in equally effective PK/PD parameters as ITI in normal weight, good renal-function patients.

Quantitative and qualitative control of cytotoxic preparations by HPLC-UV in a centralized parenteral preparations unit.

The constantly growing incidence of cancer and long-term treatment are leading to an increasing number of cytotoxic preparations in hospital pharmacies. Security and quality standards of cytotoxic preparations are essential to assure treatment efficiency and limit iatrogenic toxicity. In order to secure the process of cytotoxic preparations; we decided to install a quantitative and qualitative High Performance Liquid Chromatography (HPLC) control of cytotoxic preparations carried inside our pharmacotechnic unit. A 100 microl sample of each preparation was assayed by HPLC with ultraviolet/visible-diode array detection, which enabled the identification of all cytotoxic agents thanks to their characteristic UV spectra. We developed rapid and specific HPLC assays that determined qualitatively and quantitatively the presence of 21 different cytotoxic agents in less than 3.5 min. A fifteen per cent tolerance from the theoretical concentration was chosen in agreement with preparation and dosage bias, and a first period control of more than 4400 preparations revealed that around 7.7% preparations did not conform. The main objective of these controls was to avoid the administration of defective chemotherapies to patients and finally to use their results to identify error factors; as a result we will take corrective measures in order to reduce error frequency.

Determination of levofloxacin in plasma, bronchoalveolar lavage and bone tissues by high-performance liquid chromatography with ultraviolet detection using a fully automated extraction method.

The aim of this study was to develop a specific and sensitive high-performance liquid chromatographic (HPLC) assay for the determination of levofloxacin in human plasma, bronchoalveolar lavage and bone tissues. The sample extraction was based on a fully automated liquid-solid extraction with an OASIS cartridge. The method used ultraviolet detection set at a wavelength of 299 nm and a separation with a Supelcosil ABZ+ column. The assay has been found linear over the concentration range 0.25-25 microg/ml for levofloxacin in plasma, 1-6 microg/ml in bronchoalveolar lavage and 0.5-10 microg/g for bone tissues and it provided good validation data for accuracy and precision. The assay will be applied to determine the penetration of levofloxacin in human bronchoalveolar lavage (BAL) and bone tissues during pharmacokinetic steady state.

Diffusion of oral and intravenous 400 mg once-daily moxifloxacin into lung tissue at pharmacokinetic steady-state.

The degree of penetration of an antibiotic into the infection site is an important factor for its therapeutic efficacy, particularly in respiratory tract infections. In the present study, we examined the lung tissue diffusion of moxifloxacin at a dose of 400 mg administered intravenously or orally once-daily, and the results were correlated to microbiological data to estimate the clinical efficacy of moxifloxacin in lower community-acquired respiratory infections. This was a prospective, randomized, parallel-group trial, open-label, single-center study. Patients undergoing lung surgery for bronchial cancer which necessitates the removal of an anatomical piece of lung tissue were randomized into twelve treatment groups, dependent upon the time of surgery and the moxifloxacin formulation, i.v. or oral, administered. During surgery, one blood sample was taken at the time of tissue collection to determine moxifloxacin plasma concentration. At the same time, tissue samples were taken by pulmonary exeresis. A validated new high performance liquid chromatography assay was used to determine moxifloxacin concentrations in plasma and lung tissue. A total of 49 patients (25 for i.v. administration, 24 for oral administration, 44 men and 5 women, mean age, 61 years, mean body weight, 72 kg, mean creatinine clearance was 84 ml/min/1.73 m2) were enrolled. The mean +/- SD steady-state moxifloxacin ratios between lung and plasma concentrations were respectively: 3.53 +/- 1.89 and 4.36 +/- 1.48 for i.v. and oral administration. The mean steady-state moxifloxacin maximal lung concentrations (Cmax) were respectively 12.37 microg/g and 16.21 microg/g for i.v. and oral administration. Moxifloxacin both intravenously and orally exhibits high penetration in lung tissue, with tissue concentrations far above the MIC90s for most of the susceptible pathogens commonly involved, thus underlining its suitability for the treatment of community-acquired, lower respiratory tract infections.