Pharmacokinetics and Comparative Pharmacology of Cefoxitin and Cephalosporins

Abstract

Features of the distribution, metabolism, elimination, and pharmacokinetics of the cephalosporins and cefoxitin must be considered when concentrations of these drugs in biological fluids are interpreted. The extensive (∼86%) binding of cefazolin to plasma protein may account for the smaller volume of distribution and slower rate of renal clearance than are observed for cefoxitin, which is less extensively (73%) bound to protein. Results of microbiological assays of drug in urine may be influenced by the extent of metabolism of the drugs, which is 33% for cephalothin but <270 for cefoxitin. Elimination of cephalosporins and cefoxitin occurs by both glomerular filtration and tubular secretion and can be inhibited by the concurrent administration of probenecid. The pharmacokinetics of cefoxitin may be described by a linear, twocompartment, open model that has been used to predict levels of drug achieved in serum and urine after various dose regimens, including administration by intravenous bolus or infusion. The bioavailability of intramuscularly administered cefoxitin is equivalent to that of intravenously administered cefoxitin and is 90% complete within 3–4 hr after the dose is given.