Cephalosporins, protein binding effects

Mechanism of Action A second-generation cephalosporin that binds to bacterial cell membranes and inhibits cell wall synthesis. Therapeutic Effect Bactericidal. Pharmacokinetics Well absorbed from the GI tract. Protein binding 25%. Widely distributed. Primarily excreted unchanged in urine. Moderately removed by hemodialysis. Half-life 0.6-0.9 hr (increased in impaired renal function). 

Mecftantsm of Action A third-generation cephalosporin that binds to bacterial cell membranes. Therapeutic Effect Inhibits synthesis of bacterial cell wall. Bactericidal. Pharmacokinetics Widely distributed, including cerebrospinal fluid (CSF). Protein binding 82%-93%. Metabolized and excreted in kidney and urine. Removed by hemodialysis. Half-life 1.6-2.4 hr (half-life is increased with impaired renal function). 

Ceftiofur and its active metabolite desfuroylceftiofur distribute differently to the other cephalosporins because of their high degree of protein binding. Reversible covalent bonding with plasma and hssue proteins produces lower than expected free concentrations of ceftiofur and desfuroylceftiofur following the administration of clinically effective doses. Tissue chamber studies have shown that concentrations of parent drug and active metabolite are higher in infected than in normal tissues. 

The P-lactam antibiotics continued to be the cynosure of synthesis. Some structure-activity relationships of peni-cillins O and cephalosporins 2 v/ere discussed. Timely reports aimed primarily toward the evaluation of the newer highly serum-bound penicillins dealt with the controversial relationship of drug-serum protein binding to clinical antimicrobial effectiveness. 3,14... 

The monohactams, like pcncillins and cephalosporins, interfere with the synthesis of bacterial cell walls. /l-Lactani antibiotics bind to a series of penicillin-binding proteins (PBPs) on the cytoplasmic membrane and their antibacterial effect is believed to result from inhibition of a subset of these PBPs known as peplidoglycan transpeptidases. 

Effect of 7a-Methoxy Substitution in Cephalosporins upon Their Affinity for Penicillin-Binding Proteins ... 

TABLE XXV Effect of 7a-Methoxy Substitution of Cefuroxime, Cephamandole, Cephapirin, and Cephalosporin 87/359 upon Their Affinity for the Penicillin-Binding Proteins of Escherichia coli DCO" ... 

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