Serum and sputum concentrations of ceftazidime in patients with cystic fibrosis

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/1 respectively with corresponding mean concentrations in sputum of 2–7, 2.6 and 1.6 mg/1. 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.