PHARMACOKINETICS OF FLOMOXEF IN CHILDREN UNDERGOING CHRONIC HEMODIALYSIS

• Published in: Japanese journal of antibiotics 1993/07/25, Vol.46(7), pp.511-517
• Main Authors: SASAGAWA, FUJIO, NAKANO, TOKUSHI, MITO, YOSHIAKI, SEKINE, OSAMU
• Format: Article
• Language: Japanese
• Subjects: Adolescent; Cephalosporins - administration & dosage; Cephalosporins - pharmacokinetics; Child; Female; Humans; Injections, Intravenous; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - therapy; Male; Renal Dialysis
• ISSN: 0368-2781; 2186-5477
• DOI: 10.11553/antibiotics1968b.46.511

The pharmacokinetics of flomoxef (FMOX), an oxacephem antibiotic, were investigated in pediatric patients undergoing chronic hemodialysis. The results are summarized as follows. 1. FMOX was given intravenously in a single dose of 10mg/kg to 5 pediatric patients (ranging from 7 to 15 years of age) undergoing chronic hemodialysis. It was also given in a dose of 5mg/kg to 2 of these patients. Its concentrations in serum and urine were determined using bioassay. Pharmacokinetic analyses were performed using a two compartment open model. 2. The serum concentrations of FMOX, administered in doses of 10mg/kg or 5mg/kg on non-hemodialysis days, were 33.3±4.09μg/ml(mean±standard deviation) and 17.6μg/ml (mean) at 30 minutes after injection, 29.6±3.51μg/ml and 15.9μg/ml at 1 hour, 27.2±2.14μg/ml and 15.1μg/ml at 2 hours, 23.5±1.90μg/ml and 13.0μg/ml at 4 hours, 20.8±2.44μg/ml and 12.2μg/ml at 6 hours, 18.9±1.86μg/ml and 11.0μg/ml at 8 hours, and 9.64±1.43μg/ml and 6.16μg/ml at 24 hours, respectively. 3. The urinary concentrations of FMOX, administered in a dose of 10mg/kg, were 42.4-123μg/ml between 0-6 hours after injection, 14.1-52.5μg/ml between 6-24 hours, and 2.86-23.7μg/ml between 24-48 hours. The urinary excretion rate in the first 48 hours after injection ranged from 9.1 to 10.5%. 4. Pharmacokinetic analyses showed that k10 was 0.070±0.007hr-1, an extremely low value, T 1/2α was 0.51±0.46 hour, moderately prolonged, T1/2/3 was 15.03±1.34 hours, very prolonged, Vc was 0.23±0.03L/kg, a moderately low value, and AUC was 616.5±90.9μg·hr/ml, an extremely high value, in patients undergoing chronic hemodialysis as compared to those values in a child with normal renal function. 5. These findings suggest that FMOX should be administered intravenously once a day at a dose of 10mg/kg to pediatric patients undergoing chronic hemodialysis and that the dose may be lowered to 5mg/kg in some bacterial infections.