The pharmacokinetics of single doses of cefaclor at 250 and 375 mg and cefuroxime axetil at 250 mg administered under optimal conditions (i.e., cefuroxime axetil after food and cefaclor in the fasted state) were studied in 24 healthy male volunteers. Drug concentrations in serum were related to MICs for common respiratory tract pathogens by using data generated from a recently completed national survey. The time the concentrations in serum exceeded the MICs for Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella (formerly BranhameUla) catarrhalis were significantly greater (P < 0.05) for cefuroxime axetil at 250 mg than for cefaclor at 250 or 375 mg. With the recommended dosing regimens (cefuroxime axetil at 250 mg and cefaclor at 375 mg twice daily or cefaclor at 250 mg three times daily), cefuroxime concentrations exceed the MIC for 90% of the strains tested for a greater time period than cefaclor concentrations with either regimen. The reasons for this difference are (i) the greater potency and slower clearance of cefuroxine compared with those of cefaclor and (ii) the greater sensitivity of these pathogens to cefuroxime.

The pharmacokinetics of cefuroxime axetil suspension in 28 infants and children, ranging in age from 3 months to 12 years (mean, 23 months), were studied. Mean maximum serum cefuroxime concentrations of 3.3, 5.1, and 7.0 ,ug/ml were achieved 3.6, 2.7, and 3.1 h after the administration of doses of 10, 15, and 20 mg, respectively, of cefuroxime axetil suspension per kg of body weight together with milk or milk formula. These concentrations exceed the MICs for common respiratory tract pathogens, including j8-lactamase-producing strains of Haemophilus influenzae and Moraxella (Branhamella) catarrhalis. Following a 10-or 15-mg/kg dose, serum cefuroxime concentrations are similar to those achieved in adults following the administration of a 250-mg cefuroxime axetil tablet. There were linear relationships between dose and both maximum serum cefuroxime concentration and area under the serum drug concentration-versus-time curve. The mean half-life of cefuroxime in serum was independent of dose and ranged from 1.4 to 1.9 h. No cefuroxime axetil (intact ester) was detected in the blood. The intact ester in the urine of four children was measured; however, the amount recovered represented less than 0.1% of the administered dose.Cefuroxime axetil is the orally absorbed ester prodrug of the cephalosporin cefuroxime sodium. Since cefuroxime sodium is not absorbed orally (4), the 1-acetyloxyethyl ester was substituted for sodium on the cefuroxime molecule to increase its lipid solubility and improve its gastrointestinal absorption. After oral administration, cefuroxime axetil is absorbed and rapidly hydrolyzed by nonspecific esterases in the intestinal mucosa and portal blood (10) to produce concentrations of cefuroxime that exceed the MIC of common respiratory tract pathogens, including 3-lactamasepositive and -negative strains (1,11,12,17).A suspension formulation of cefuroxime axetil has been developed to facilitate the administration of cefuroxime axetil to pediatric patients. In healthy adult volunteers, the suspension formulation of cefuroxime axetil is less bioavailable than the tablet formulation (8). The purpose of this study was to evaluate the pharmacokinetics of cefuroxime axetil suspension in infants and children. MATERIALS AND METHODSPediatric patients, aged 3 months to 12 years, with infections which required systemic antibiotic therapy and for which cefuroxime axetil suspension was considered to be appropriate treatment were eligible for this open-label, randomized, parallel-group study. Patients receiving parenteral antibiotics for whom conversion to oral therapy was being considered were included in the study. Patients with a history of hypersensitivity reactions to beta-lactam antibiotics were excluded.The study was conducted at the Children's Hospital in Columbus, Ohio, and was approved by the institutional review board of the hospital. Written informed consent was obtained from the parents of all patients participating in the study. Each patient underwent a complete physical examination and routine clinica...

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