The pharmacokinetics of moxalactam in renal failure patients

Moxalactam is a semi-synthetic beta-lactam antimicrobial agent currently undergoing Phase III clinical trials in human subjects. In vitro studies demonstrate that moxalactam is effective against most gram-positive and gram-negative organisms, except Streptococcus, Group D. The drug is excreted almost entirely by renal mechanisms. Moxalactam is 38-to-50% plasma protein bound, based on in vitro studies. the elimination half-life of moxalactam is two to three hours in patients with normal renal function, and 19 hours in patients with end-stage renal disease. No investigations thus far have determined the hemodialyzability of moxalactam. Pharmacokinetic data of moxalactam in renal failure patients are important not only to provide adequte dosage guidelines for therapeutic efficacy, but also to prevent potential dose-related neurologic, hematologic, and renal toxicities that have been reported with other cephalosporins. The purpose of this study was: 1.) To determine the pharmacokinetic parameters of moxalactam in patients with severe renal impairment undergoing hemodialysis therapy; 2.) To determine the effect of hemodialysis on the pharmacokinetic parameters; and 3.) To develop appropriate guidelines for dosing moxalactam in hemodialysis patients.