Pharmacokinetics and tolerance of cefuroxime axetil in volunteers during repeated dosing

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...

Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 52%

Pharmacokinetics of cefuroxime axetil suspension in infants and children

Powell

James

Ossi

et al. 1991

“…Pharmacokinetic studies performed in adults have shown that cefuroxime axetil is well absorbed after oral administration; peak concentrations of cefuroxime occur in serum approximately 2 h after oral administration of tablets (2,4). In adults the peak concentrations of cefuroxime in serum and the area under the time-concentration curve (AUC) after administration of cefuroxime axetil are significantly increased when the drug is administered with food (5).…”

mentioning

confidence: 99%

Pharmacokinetics and bactericidal activity of cefuroxime axetil

Ginsburg¹,

McCracken²,

Petruska³

et al. 1985

The pharmacokinetics of cefuroxime axetil were studied in 10 adult volunteers aged 24 to 31 years (mean age, 27), 22 infants and children aged 11 to 68 months (mean age, 33 months), and 11 children aged 7 years, 7 months to 12 years, 3 months (mean age, 11 years, 1 month). Mean peak plasma concentrations of cefuroxime occurred between 90 and 120 min in all study patients and were independent of the fasting or feeding status.The areas under the concentration-time curves were significantly higher in adult volunteers who received cefuroxime axetil with milk than in those who received the drug while fasting or with applesauce. The bioavailablity of cefuroxime axetil was significantly enhanced in children by the concomitant ingestion of cefuroxime axetil and infant formula or whole milk. The areas under the concentration-time curves were 25 to 88% higher when cefuroxime axetil and milk were administered simultaneously than when the same dose was given to all fasting patients. The plasma bactericidal activities of cefuroxime against beta-lactamase-positive and -negative strains of Haemophilus influenzae and Staphylococcus aureus at the time of peak plasma concentrations were independent of feeding status and were similar in adults and in children. Against these strains, 52% of the children and 38% of the adults had peak bactericidal levels of 1:8 or greater.

“…Antacids also had no effect on the cephalosporins cefopril, cefixime, and cephalexin (16,23), as well as amoxicillin or amoxicillin-clavulanic acid (9,27). A significant reduction of bioavailability was, however, observed for cefpodoxime proxetil after coadministration with antacids or famotidine, an H 2 antagonist (22,26), which was thought to be due to the pH-dependent reduction of tablet disintegration and drug solubility in the gut lumen. The pharmacokinetics of azithromycin were only slightly impaired by antacids (reduced peak levels) (12); those of roxithromycin were not affected (4).…”

mentioning

confidence: 93%

Lack of Pharmacokinetic Interaction between Linezolid and Antacid in Healthy Volunteers

Grunder¹,

Zysset-Aschmann²,

Vollenweider³

et al. 2006

Several antibiotics show significant pharmacokinetic interactions when they are given orally concomitantly with antacids. The objective of this study was to evaluate the effects of antacid (containing magnesium) on the pharmacokinetics of linezolid. A single dose of 600 mg linezolid was given orally alone and 10 min after administration of the antacid Maalox 70mVal, which contains 600 mg magnesium hydroxide and 900 mg aluminum hydroxide, to nine healthy males and nine healthy females in a crossover and randomized study. Linezolid plasma concentrations were determined by high-performance liquid chromatography, and pharmacokinetic parameters were calculated for both treatments. . However, a significant sex difference was observed for AUC, C max , V/F, and CL/F; and these differences could be almost completely explained by the differences in body weight between males and females. No clinically relevant adverse effects were detected under either condition. The coadministration of antacids had no effect on the pharmacokinetics of linezolid. This demonstrates that the oral absorption of linezolid was not affected by the presence of antacids containing magnesium hydroxide and aluminum hydroxide. Antacids can be safely administered together with linezolid.