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Pharmacokinetics and cerebrospinal fluid concentrations of cefixime in infants and young children
M C Nahata1, V M Kohlbrenner, W J Barson
1College of Pharmacy, Ohio State University, Columbus 43210.
Insights
Cefixime shows good pharmacokinetic properties and cerebrospinal fluid (CSF) penetration in infants and young children. This study suggests cefixime as a viable alternative antimicrobial for pediatric infections.
Area of Science:
- Pharmacology
- Pediatrics
- Infectious Diseases
Background:
- Limited pharmacokinetic and cerebrospinal fluid (CSF) penetration data exist for cefixime in infants and young children.
- Cefixime is a third-generation cephalosporin antibiotic used for various infections.
Purpose of the Study:
- To evaluate cefixime pharmacokinetics and CSF penetration in infants and young children.
- To determine cefixime's suitability as an alternative antimicrobial in pediatric populations.
Main Methods:
- A single dose of cefixime (8 mg/kg) was administered to 18 pediatric patients (2-22 months old).
- Blood and CSF samples were collected at timed intervals post-administration.
- Cefixime concentrations were quantified using high-performance liquid chromatography.
Main Results:
- Peak serum concentrations of cefixime ranged from 0.85 to 6.2 µg/ml, with a mean of 3.1 µg/ml.
- CSF concentrations ranged from 0.02 to 0.57 µg/ml, with a mean of 0.22 µg/ml in meningitis patients.
- The mean CSF/serum concentration ratio was significantly higher in meningitis patients (11.7) compared to shunt placement patients (5.4).
Conclusions:
- Cefixime demonstrates favorable pharmacokinetic profiles and adequate CSF penetration in infants and young children.
- The drug's peak serum concentrations exceed minimum inhibitory concentrations for common pathogens.
- Cefixime can be considered an alternative antimicrobial for pediatric respiratory and urinary tract infections.
Abstract:
Limited data are available about cefixime pharmacokinetics and cerebrospinal fluid (CSF) penetration in infants and young children. Ten patients with bacterial meningitis and 8 undergoing CSF shunt placement, aged 2-22 months (mean 9.5 +/- 6.5 months), were given a single dose of cefixime suspension, 8 mg/kg, before undergoing a routine lumbar puncture. Patients were fasted for 2 h before and 2 h after drug administration. Blood samples were collected just before drug administration (0 h) and at 1, 2, 3, 4, 6, 8 h; CSF was obtained at 1-8.8 h after drug administration. Cefixime was measured by a high-performance liquid chromatographic method. The peak serum concentration of cefixime ranged from 0.85 to 6.2 (mean 3.1) micrograms/ml and occurred at 2-8 h (mean 4.5). The area under the serum concentration-time curve ranged from 5.3 to 28.4 micrograms h/ml, and the elimination half-life ranged from 2.6 to 5.6 h. CSF concentrations ranged from 0.02 to 0.57 micrograms/ml. The mean CSF concentration of cefixime was 0.22 micrograms/ml in patients with meningitis and 0.10 microgram/ml in those undergoing shunt placement (p < 0.02). The mean CSF concentration/serum concentration ratio was 11.7 in patients with meningitis compared with 5.4 in those undergoing shunt procedures (p < 0.02). These data indicate that cefixime can be considered as an alternative to other antimicrobials for infants and children with respiratory and urinary tract infections, since the observed peak serum concentration exceeded the minimum inhibitory concentrations of the common pathogens by severalfold.(ABSTRACT TRUNCATED AT 250 WORDS)