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  • Title: Cefpirome clinical pharmacokinetics.
    Author: Strenkoski LC, Nix DE.
    Journal: Clin Pharmacokinet; 1993 Oct; 25(4):263-73. PubMed ID: 8261711.
    Abstract:
    Cefpirome is a new cephalosporin that exhibits similar in vitro potency to ceftazidime against Gram-negative organisms but has significantly greater in vitro potency against Gram-positive organisms. Cefpirome differs from cefotaxime in that a 3'-pyridinium moiety replaces the acetoxy moiety of cefotaxime. This structural change imparts greater beta-lactamase stability, increases the ability to penetrate the outer membrane of Gram-negative bacteria, and enhances activity against Gram-positive organisms. The pharmacokinetic properties of cefpirome are typical of cephalosporins. The drug can be administered by intravenous or intramuscular injection, but is not well absorbed after oral administration. Bioavailability following intramuscular injection exceeds 90%. Cefpirome exhibits low protein binding (approximately 10%) and has a volume of distribution similar to extracellular fluid volume. Cefpirome penetrates the prostate gland, lung, blister fluid, cerebrospinal fluid and peritoneal fluid, reaching concentrations that are similar to those achieved by other later generation cephalosporins. Approximately 80% of an intravenous dose is eliminated unchanged in the urine. No active metabolites of cefpirome have been identified. The elimination half-life of cefpirome is approximately 2 hours. Elimination appears to be primarily by glomerular filtration since the total clearance of cefpirome is approximately equal to creatinine clearance. The time during which drug concentrations exceed the minimum inhibitory concentration (MIC) represents the most clinically important pharmacodynamic parameter for beta-lactam agents. When cefpirome is administered at a dosage of 2g every 12 hours to patients without renal insufficiency [creatinine clearance 70 ml/min (4.2 L/h)], drug concentrations continuously remain above the MIC for pathogens with MIC values of < or = 2 micrograms/ml. With this dosage regimen, drug concentrations will be above the MIC for a pathogen with an MIC of 4 micrograms/ml for 80% of the dosage interval. The time above MIC for pathogens with an MIC of 8 micrograms/ml is only 60% of the dosage interval.
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