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Single-dose pharmacokinetics of ceftibuten (SCH 39720) in infants and children
G L Kearns1, M D Reed, R F Jacobs
1Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock.
Insights
Ceftibuten (CFB) demonstrates rapid absorption and predictable pharmacokinetics in pediatric patients, with age influencing drug clearance. This oral cephalosporin shows potential for treating common pediatric infections like otitis media and respiratory tract infections.
Area of Science:
- Pharmacology
- Pediatric Infectious Diseases
Background:
- Ceftibuten (CFB) is a novel oral cephalosporin with broad-spectrum activity against common pediatric pathogens.
- Its pharmacokinetic profile in children is crucial for determining optimal dosing for infections such as otitis media and respiratory/urinary tract infections.
Purpose of the Study:
- To evaluate the pharmacokinetic characteristics of Ceftibuten (CFB) in pediatric patients.
- To assess the influence of age and renal function on CFB disposition in children.
Main Methods:
- A multicenter study involving 49 pediatric patients (6 months to 17 years) with normal organ function.
- Single oral doses of 4.5 or 9.0 mg/kg CFB were administered, with serial blood and urine samples collected for analysis.
- High-performance liquid chromatography (HPLC) was used to quantify CFB concentrations in plasma and urine.
Main Results:
- CFB was rapidly absorbed, with a mean time to peak concentration of 140 minutes and peak plasma concentrations ranging from 5.0 to 19.0 mg/liter.
- Average pharmacokinetic parameters included an elimination half-life of 2.0 hours and total plasma clearance (CL/F) of 2.5 ml/min/kg.
- Significant negative correlations were observed between patient age and CFB elimination half-life and clearance, indicating age-dependent disposition.
Conclusions:
- Ceftibuten exhibits favorable pharmacokinetic properties in pediatric patients, supporting its use in treating common infections.
- Age significantly impacts CFB clearance, with younger children showing higher clearance rates.
- Appreciable nonrenal clearance of CFB occurs in children, differing from adult data.
Abstract:
Ceftibuten (CFB), a new broad-spectrum cephalosporin for oral administration, possesses potent activity in vitro against a wide range of gram-negative and certain gram-positive pathogens frequently encountered in pediatric patients. Its antimicrobial spectrum and dosage formulation suggest a use for CFB in the treatment of otitis media and upper and lower respiratory and urinary tract infections in infants and children. To assess the pharmacokinetic characteristics of CFB in pediatric patients, we completed a multicenter investigation of 49 children (26 females) between the ages of 6 months and 17 years who had normal hepatic and renal functions and no evidence of chronic disease. Pharmacokinetic parameters were determined from repeated blood samples (n = 12) and, when possible, quantitative urine collections (n = 7) obtained over a 12- to 24-h period following a single oral CFB dose of either 4.5 or 9.0 mg/kg of body weight. CFB was quantitated from plasma and urine samples by using a sensitive, microanalytical high-pressure liquid chromatography method. The drug was rapidly absorbed (mean time to maximum concentration in serum = 140 min) and produced apparent peak concentrations in plasma (Cmax) ranging from 5.0 to 19.0 mg/liter. Average CFB pharmacokinetic parameters (+/- standard deviations) were as follows: apparent elimination half-life, 2.0 +/- 0.5 h; mean residence time, 3.9 +/- 1.1 h; apparent steady-state volume of distribution, 0.4 +/- 0.2 liter/kg; and apparent total plasma clearance (CL/F), 2.5 +/- 0.9 ml/min/kg. No significant differences in any of the pharmacokinetic parameters were observed between the two dosing groups. Significant (P < 0.05) negative correlations were found between patient age and CFB elimination half-life and CL/F and between the estimated creatinine clearance and renal clearance and CL/F. Apparent age dependence of CFB disposition was also reflected by a greater CL/F in children from 0.5 to less than or equal 5 years of age (3.1 +/- 1.1 ml/min/kg) than in children > 10 years of age (2.0 +/- 0.6 ml/min/kg; P < 0.005). The increased CL/f for CFB (3.0 +/- 0.5 ml/min/kg) was corroborated by a validation study performed with 11 infants (1.0 +/- 0.5 ml/min/kg) with CL/F for 19 subjects suggested that appreciable nonrenal clearance (1.3 +/- 0.6 ml/min/kg) of CFB occurred in children, a finding different from preliminary data for adults.