Serum and sputum concentrations of ceftazidime in patients with cystic fibrosis

Abstract

The pharmacokinetic parameters of ceftazidime were assessed in six cystic fibrotic patients during eight courses administered for acute exacerbations of pulmonary infection. In order to assess the initial and steady state concentrations of ceftazidime at a dose of 35 mg/kg and to determine the levels found after a higher dose, each ten day course of ceftazidime consisted of eight doses of 35 mg/kg followed by 22 doses of 50 mg/kg, all administered at 8-hourly intervals. Samples of blood and sputum were collected following the 1st, 8th and 9th doses for ceftazidime assay. The mean peak serum concentrations of ceftazidime were 97, 110 and 147 mg/l respectively with corresponding mean concentrations in sputum of 2.7, 2.6 and 1.6 mg/l. The mean clearance rate was calculated on a two compartment model to be 197 ml/min/50 kg lean body mass, the mean volume of distribution was 281/50 kg lean body mass and the mean half life was 1.57 h. There were large inter-patient differences in the pharmacokinetic parameters, however, which suggests that the clinical condition of the patient affects the pharmacokinetics of ceftazidime in cystic fibrosis. In all the patients, even after the doses of 50 mg/kg, the trough serum concentrations were low. Samples of blood were also collected for adverse effects before, during and after each course; there was no evidence of renal, hepatic or haematological changes in response to the drug.

Polymyxin B Pharmacokinetics in Adult Cystic Fibrosis Patients

“…A number of studies of other drugs have demonstrated that patients with CF frequently display different PK parameters compared to patients without CF (e.g., Cl, Vd) . In our analysis, we found similar overall PK parameter estimates between both patient populations when using NCA.…”

Population Pharmacokinetic Comparison and Pharmacodynamic Breakpoints of Ceftazidime in Cystic Fibrosis Patients and Healthy Volunteers

“…Our results on terminal half-life (Table 2) were in good agreement with the shorter terminal half-life of 1.5 Ϯ 0.2 h in CF patients compared to 1.76 Ϯ 0.2 h in healthy volunteers reported by Leeder et al (44). The reported average half-lives in juvenile to adult CF patients range between 1 and 2 h (41,47,50,56,58,68,72,76).…”

Sputum antibiotic concentrations: Implications for treatment of cystic fibrosis lung infection

“…Ceftazidime and tobramycin concentrations in serum and in sputum were determined by high performance liquid chromatography (HPLC) using modifications of previously described methods. 16,17 Bacterial Isolation and Susceptibility Testing Bacteria were cultured from the sputum samples collected from patients on admission to hospital, prior to commencing antibiotic treatment. The sputum samples were liquefied by incubation with sputolysin for 15 min and serial tenfold dilutions prepared in sterile phosphate buffered saline.…”