Pharmacokinetic properties of the cephalosporins

Most cephalosporins can only be administered parenterally. Among agents that are absorbed from the gastrointestinal tract, those with bioavailabilities of 85 to 90% include cefroxadine, cefadroxil, cefsumide, cephalexin, cephradine, cephacetrile, and cefazaflur. Most cephalosporins are eliminated rapidly, with serum half-lives (t1/2s) of 1 to 2 hours. Exceptions are cefonicid with a t1/2 of 4.4 hours, cefpiramide with a t1/2 of 5.0 hours, and cefotetan with a t1/2 of 3.5 hours. The longest half-life is shown by ceftriaxone with a t1/2 of 8.5 hours. Cephalosporins are eliminated mostly by the kidneys, some with a substantial contribution from active tubular secretion, which is blocked by probenecid. The degree of metabolism varies. Only a few cephalosporins have a high biliary elimination. For example, with intravenously administered cefoperazone, about 70% appears in bile. High biliary elimination is also observed with cefmenoxime, ceftriaxone, cefbuperazone, and latamoxef (moxalactam). Because these are not appreciably absorbed from the gastrointestinal tract, the consequence is high intraintestinal concentrations of the drugs and a marked ensuing depression of the normal microflora with simultaneous emergence of resistant bacteria. The untoward ecological impact may even lead to Clostridium difficile-associated enterocolitis.