Cloxacillin absorption and disposition in cystic fibrosis

Because of reports of lowered antibiotic serum concentrations in patients with cystic fibrosis (CF), a bioavailability and pharmacokinetic study of cloxacillin was conducted in 12 control and 16 patients with CF after intravenously and orally administered doses of cloxacillin 25 mg/kg. The patients had mild to moderate CF and were in stable condition. Significantly lower serum concentrations in CF were a result of a 78% increase in total body clearance (P less than 0.005) and a 38% increase in the apparent volume of distribution (P less than 0.025). The bioavailability in CF (0.50) was not significantly different than in controls (0.38), but more variability was seen in the group with CF. After the intravenously given dose the fraction of cloxacillin excreted in the urine unchanged was similar in controls (0.644) and patients with CF (0.547). Compared with that in the control subjects, the mean renal clearance in patients with CF was 30% greater (P less than 0.10) and the nonrenal clearance was 144% greater (P less than 0.07). Enhanced nonrenal clearance explains most of the demonstrated difference between serum concentrations in controls and patients with CF after identical weight-adjusted doses. The data suggest enhanced cloxacillin biotransformation in CF.