Ceftazidime disposition in acute and stable cystic fibrosis.

Ceftazidime disposition after an intravenous dose of 50 mg/kg infused over 20 min was followed in 10 subjects with cystic fibrosis (CF) hospitalized with acute pulmonary exacerbations and in 10 healthy subjects. Serum ceftazidime elimination t 1/2 decreased from 105.3 +/- 12.4 min (mean +/- SD) in controls to 90.0 +/- 11.1 min in subjects with CF. Calculated distribution volumes were both larger in subjects with CF. When normalized for body surface area, total body clearance (Cl) was 41.9% greater in the CF group (142.4 +/- 16.9 and 100.5 +/- 10.3 ml/min/1.73 m2). Normalization for body weight revealed 64.8% greater Cl in subjects with CF. Fraction of dose recovered in urine was of the same order for each group, while renal clearance (ClR) was 40.9% greater in the subjects with CF (130.1 +/- 11.4 and 92.7 +/- 11.6 ml/min/1.73 m2). Five subjects with CF were restudied while infection-free 119 to 219 days after the original study day. With the exception of a 10% increase in the volume of distribution at steady state while infection-free, kinetic parameters were much the same. No changes in Cl or ClR were evident from one study day to the next. Acute pulmonary infection does not appear to alter ceftazidime clearance in CF. The mechanism underlying increased ceftazidime Cl and ClR in CF is not apparent from the present data.

High-pressure liquid chromatographic analysis of ceftazidime in serum and urine.

A rapid and sensitive high-pressure liquid chromatographic procedure was developed for quantitative analysis of a new semisynthetic cephalosporin, ceftazidime, in serum and urine. A good linear relationship was established between peak height and the amount of ceftazidime injected over a concentration range of 1.9 to 30 micrograms/ml. Recovery was approximately 90% at concentrations of 3, 15, and 30 micrograms/ml. The method is specific for ceftazidime, with no interference noted from 11 other beta-lactam antibiotics tested. The assay is accurate, reproducible, and useful for pharmacokinetic studies in humans as demonstrated in two subjects.

A rapid high performance liquid chromatographic procedure for the analysis of cloxacillin and/or nafcillin in serum.

A rapid, reliable procedure for the analysis of cloxacillin and/or nafcillin in 100 microliter of serum or plasma is described. Percentage analytical recovery of cloxacillin, nafcillin, and internal standard (5-(p-hydroxyphenyl)-5-phenylhydantoin) were 94, 91, and 85%, respectively. The between-day precision of the method at cloxacillin concentrations of 2, 8, and 20 mg/liter was 14.7, 11.6, and 10.3%, respectively. At identical serum concentrations, the values obtained for nafcillin were 15.3, 12.4, and 12.2%, respectively. The method will be used to study the pharmacokinetics of both drugs in patients with cystic fibrosis who are on long-term therapy. Preliminary data providing the i.v. half-life, clearance, and volume of distribution are presented for two normal individuals.