OBJECTIVE: Information about the pharmacokinetics of fluoroquinolone antibiotics in high risk children is scant. This study examined the disposition of sequentially administered intravenous and oral ciprofloxacin, as well as provided dosing recommendations, for the treatment of acute pulmonary exacerbations in pediatric cystic fibrosis patients. METHODS: After enrollment in a Food and Drug Administration approved protocol, the pharmacokinetic profiles of ciprofloxacin (CIP) administered to 18 children with cystic fibrosis (ages 5 to 17 years) were studied at steady state after sequentially administered intravenous (10 mg/kg every 8 h) and oral (20 mg/kg every 12 h) doses. All children enrolled met published criteria for exacerbation of Pseudomonas aeruginosa lung infection and received CIP intravenously (given as a 1-h infusion) followed by oral administration, each for a minimum of 3 days. All patients were at a mild to moderate stage in their disease with National Institutes of Health scores between 37 and 83. Blood samples were drawn at 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 (after both i.v. and oral dosing) and 12 h (oral only) after CIP administration. CIP serum concentrations were determined by high performance liquid chromatography. RESULTS: After oral CIP mean +/- SD peak serum concentrations and peak times were 3.7 +/- 1.4 mg/l and 2.5 +/- 1.8 h, respectively, compared with 5.0 +/- 1.5 mg/l and 1.0 +/- 0.3 h after completion of the i.v. infusion. Maximum concentrations, when normalized for dose, were 0.52 +/- 0.12 and 0.19 +/- 0.07 mg/l/kg after i.v. and oral dosing, respectively. The 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 i.v. and oral administration, respectively, and did not differ by age. Total clearance after i.v. administration was 19.5 +/- 10.9 liters/h. No significant CIP-related adverse effects were noted. CONCLUSIONS: CIP doses of 30 mg/kg/day i.v. and 40 mg/kg/day orally must be administered to children with cystic fibrosis to achieve optimal therapeutic concentrations.
OBJECTIVE: Information about the pharmacokinetics of fluoroquinolone antibiotics in high risk children is scant. This study examined the disposition of sequentially administered intravenous and oral ciprofloxacin, as well as provided dosing recommendations, for the treatment of acute pulmonary exacerbations in pediatric cystic fibrosispatients. METHODS: After enrollment in a Food and Drug Administration approved protocol, the pharmacokinetic profiles of ciprofloxacin (CIP) administered to 18 children with cystic fibrosis (ages 5 to 17 years) were studied at steady state after sequentially administered intravenous (10 mg/kg every 8 h) and oral (20 mg/kg every 12 h) doses. All children enrolled met published criteria for exacerbation of Pseudomonas aeruginosa lung infection and received CIP intravenously (given as a 1-h infusion) followed by oral administration, each for a minimum of 3 days. All patients were at a mild to moderate stage in their disease with National Institutes of Health scores between 37 and 83. Blood samples were drawn at 0, 0.5, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0 (after both i.v. and oral dosing) and 12 h (oral only) after CIP administration. CIP serum concentrations were determined by high performance liquid chromatography. RESULTS: After oral CIP mean +/- SD peak serum concentrations and peak times were 3.7 +/- 1.4 mg/l and 2.5 +/- 1.8 h, respectively, compared with 5.0 +/- 1.5 mg/l and 1.0 +/- 0.3 h after completion of the i.v. infusion. Maximum concentrations, when normalized for dose, were 0.52 +/- 0.12 and 0.19 +/- 0.07 mg/l/kg after i.v. and oral dosing, respectively. The 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 i.v. and oral administration, respectively, and did not differ by age. Total clearance after i.v. administration was 19.5 +/- 10.9 liters/h. No significant CIP-related adverse effects were noted. CONCLUSIONS:CIP doses of 30 mg/kg/day i.v. and 40 mg/kg/day orally must be administered to children with cystic fibrosis to achieve optimal therapeutic concentrations.
Authors: S Payen; R Serreau; A Munck; Y Aujard; Y Aigrain; F Bressolle; E Jacqz-Aigrain Journal: Antimicrob Agents Chemother Date: 2003-10 Impact factor: 5.191