Activity, stability, and pharmacology of the epimers of moxalactam.
By an agar-dilution procedure, the minimal inhibitory concentrations of R, S, and R + S epimers of moxalactam were determined for 23 commonly isolated organisms. Generally the R epimer was twice as active as the S epimer; however, against Pseudomonas aeruginosa the two were equally active. The stability of the epimers and of the R + S mixture in saline and serum was studied by high-pressure liquid chromatography. Each epimer was stable at -20 C. The interconversion half-life in serum at 37 C, 22 C, and 4 C was 1.5, 4.8, and 13 hr, respectively, for R and 1.5, 11, and 43 hr for S. In buffer both epimers were more stable. In buffered saline the final mixture of R:S was 50:50, if one started with either the R or the S epimer. In serum, however, the R:S ratio of the mixture at equilibrium was 45:55. In patients with normal renal function the ratio of R:S in serum at 2 hr was 0.69 and at 8 hr, 0.55. In patients with severe renal failure the R:S ratio at 2 hr was approximately 0.9 and at 6 hr, 0.85. Probably, in renal failure, time is sufficient for re-equilibration of the epimeric mixture, and hence there is little alteration in the R:S ratio with time.
D001419:Bacteria / Q000187:drug effects; D002511:Cephalosporins / Q000494:pharmacology*; D002513:Cephamycins / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000378:metabolism; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009070:Moxalactam; D013237:Stereoisomerism
D002511:Cephalosporins; D002513:Cephamycins; D003404:Creatinine; D009070:Moxalactam