PHARMACOKINETIC DISPOSITION OF SEQUENTIAL INTRAVENOUS ORAL CIPROFLOXACIN IN PEDIATRIC CYSTIC-FIBROSIS PATIENTS WITH ACUTE PULMONARY EXACERBATION/

Objective, information about the pharmacokinetics of fluoroquinolone a ntibiotics in high risk children is scant. This study examined the dis position of sequentially administered intravenous and oral ciprofloxac in, as well as provided dosing recommendations, for the treatment of a cute pulmonary exacerbations in pediatric cystic fibrosis patients. Me thods. After enrollment in a Food and Drug Administration approved pro tocol, the pharmacokinetic profiles of ciprofloxacin (CIP) administere d to 18 children with cystic fibrosis (ages 5 to 17 years) were studie d at steady state after sequentially administered intravenous (10 mg/k g every 8 h) and oral (20 mg/kg every 12 h) doses. All children enroll ed met published criteria for exacerbation of Pseudomonas aeruginosa l ung infection and received CIP intravenously (given as a 1-h infusion) followed by oral administration, each for a minimum of 3 days. All pa tients mere at a mild to moderate stage in their disease with National Institutes of Health scores between 37 and 83. Blood samples were dra wn at 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 (after both IV and oral dos ing) and 12 h (oral only) after CIP administration, CIP serum concentr ations were determined by high performance liquid chromatography. Resu lts. After oral CIP mean +/- SD peak serum concentrations and peak tim es were 3.7 +/- 1.4 mg/l and 2.5 +/- 1.8 h, respectively, compared wit h 5.0 +/- 1.5 mg/l and 1.0 +/- 0.3 h after completion of the iv infusi on. Maximum concentrations, when normalized for dose, were 0.52 +/- 0. 12 and 0.19 +/- 0.07 mg/l/kg after iv and oral dosing, respectively. T he mean bioavailability of oral CIP for all patients was 76%; younger patients appeared to absorb oral CIP less than older subjects, 68% vs, 95%, respectively, For all patients elimination half-lives were 2.6 /- 0.6 and 3.4 +/- 0.7 h after iv and oral administration, respectivel y, and did not differ by age. Total clearance after iv administration was 19.5 +/- 10.9 liters/h. No significant CIP-related adverse effects were noted. Conclusion. CIP doses of 30 mg/kg/day iv and 40 mg/kg/day orally must be administered to children with cystic fibrosis to achie ve optimal therapeutic concentrations.