Pharmacokinetic analysis of flomoxef in children undergoing cardiopulmonary bypass and modified ultrafiltration.
OBJECTIVE
Cardiopulmonary bypass (CPB) induces changes in the pharmacokinetics of drugs. The purpose of this study was to model the pharmacokinetics of flomoxef, a cephalosporin antibiotic, in pediatric cardiac surgery.


METHODS
Each patient received a flomoxef dose of 30 mg/kg as a bolus after the induction of anesthesia and an additional dose (1 g for a child weighing < 10 kg, 2 g for > or = 10 kg) was injected into the CPB prime. Modified ultrafiltration (MUF) was routinely performed. Blood samples, urine, and ultrafiltrate were collected. In seven patients (group I), serum flomoxef concentration-time courses were analyzed by a modified two-compartment model. Utilizing the estimated parameters, serum concentrations were simulated in another eight patients (group II).


RESULTS
The initiation of CPB resulted in an abrupt increase in serum flomoxef concentrations in group I; however, concentrations declined biexponentially. The amount of excreted flomoxef in the urine and by MUF was 47% +/- 8% of the total administered dose. In group II, an excellent fit was found between the values calculated by the program and the observed serum concentrations expressed; most of the performance errors were <1.0. There was no difference in any kinetic parameter between group I and groups I + II (n = 15).


CONCLUSIONS
The pharmacokinetics of flomoxef in children undergoing CPB and MUF were well fitted to a modified two-compartment model. Using the kinetic data from this study, the individualization of dosage regimens for prophylactic use of flomoxef might be possible.
Masuda
Zenichi
Z
Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan. zenyan@aol.com
Kurosaki
Yuji
Y
Ishino
Kozo
K
Yamauchi
Keita
K
Sano
Shunji
S
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D002511:Cephalosporins / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006440:Hemofiltration; D006801:Humans; D007223:Infant; D008297:Male
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C045693:flomoxef