quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of cefuroxime as well as the other cephalosporins and penicillins against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefuroxime's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Cefuroxime possesses activity against both Gram-positive and Gram-negative bacteria. The drug retains antibacterial activity in the presence of certain beta-lactamases, both penicillinase and cephalosporinase; however hydrolysis by other beta-lactamases, alteration of the PBP, and decreases permeability results in resistance to cefuroxime.
PHARMACOKINETICS
Cefuroxime is administered intravenously and intramuscularly as the sodium salt and orally as cefuroxime axetil. Approximately 33—50% of the circulating cefuroxime is protein-bound. It is distributed into most body tissues and fluids including gallbladder; liver; kidney; bone; uterus; ovary; sputum; bile; and peritoneal, pleural, and synovial fluids. It penetrates inflamed meninges and reaches therapeutic levels within the CSF. It does cross the placenta. Cefuroxime is largely excreted unchanged into the urine via glomerular filtration and tubular secretion. A small percentage is excreted in breast milk. The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Elimination half-life is 1—2 hours in patients with normal renal function. The axetil portion of cefuroxime axetil is metabolized to acetic acid and acetaldehyde.
Oral Route
Cefuroxime axetil is rapidly hydrolyzed in the intestinal mucosa, with 37—52% of an oral dose reaching the systemic circulation as cefuroxime. Peak serum levels of cefuroxime after administration of cefuroxime axetil occur within 2 hours following an oral dose. Cefuroxime axetil oral suspension was not bioequivalent to cefuroxime axetil tablets when tested in healthy adults. The tablet and powder for oral suspension formulations are NOT substitutable on a milligram-per-milligram basis. The AUC for the suspension averaged 91% of that for the tablet, and the peak plasma concentration (Cmax) for the suspension averaged 71% of the peak plasma concentration of the tablets. Absorption of the tablet is greater when taken after food (absolute bioavailability of tablets increases from 37% to 52%); despite this difference in absorption, the clinical and bacteriologic responses were independent of administration technique and the tablets may be taken with or without food. All pharmacokinetic and clinical studies using the suspension formulation were conducted in the fed state; the suspension should thus be administered with food.
Intravenous Route
Following intravenous (IV) doses of 750 mg and 1.5 g of cefuroxime sodium to adults, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic ser |
