Ceftazidime in cystic fibrosis: pharmacokinetics and therapeutic response

Abstract

The pharmacokinetics of ceftazidime were assessed following a single-dose in 20 patients (8 to 30 years) with cystic fibrosis. All patients received 50 mg/kg (0.9 to 3.5 g) bolus over 30 to 60 sec. Multiple timed samples were obtained over 8 h and analysed by a sensitive HPLC technique. Two-compartment pharmacokinetic analysis revealed means (+/- S.D.) T 1/2 alpha, 0.45 (0.20) h; T 1/2 beta, 1.74 (0.63) h; Vd, 270.0 (50.0) ml/kg; Vc, 190.0 (50.0) ml/kg and Cl beta, 133.7 (22.8) ml/min/1.73 m2. Probenecid pretreatment in six patients was without effect on T 1/2 beta and Cl beta. Urinary excretion was (% of dose) 0 to 2 h, 65.4 (11.1); 2 to 4 h, 14.9 (3.4) and 4 to 8 h, 9.8 (5.8). Ceftazidime was used to treat pulmonary exacerbations in 12 adult cystic fibrosis patients with multiply-resistant Pseudomonas species. Each patient received 2 g iv 8-hourly for 14 to 35 days. Ten of 12 patients showed dramatic improvement as determined by increased appetite and weight gain and arterial pCO2. No hepatic, renal or bone-marrow toxicity was noted. Ceftazidime is an effective antipseudomonal agent possessing favourable pharmacokinetic characteristics with potential use in the treatment of pulmonary exacerbations in cystic fibrosis.