Comparative Pharmacokinetics and Clinical Experience with a New Cephalosporin-Derivative: Cefazolin

Abstract

In a cross-over study in 12 normal individuals, the pharmacokinetic parameters of cefalotin, cefradine and cefazolin were determined after intravenous injection of 1,000 mg of each substance. The microbiological activities in urine and serum were determined using the agar diffusion test; the pharmacokinetic data were calculated by a computer system on the basis of a Fortran programme. Cefazolin has significantly higher serum concentrations than the other two cephalosporins, distinctly longer serum half-lives, higher protein binding, and smaller apparent volumina of distribution. In 36 inpatients with mainly chronical and acute infections of the urinary tract, we tested the antibacterial effectivity, the compatibility, and the application modalities of cefazolin. In 29 patients we had a satisfactory clinical result, in 25 cases we achieved the elimination of bacteria by the end of the therapy. The compatibility of cefazolin was good; apart from a minor, reversible, liver-specific increase in enzymes in 6 patients, no side effects could be detected.

Comparative Pharmacokinetics of Cefazolin, Cephalothin, Cephacetril, and Cephapirine after Intravenous Administration

“…The present value of AUC after 0.5 g cefazolin was slightly higher than that reported by L avillaureix et al [9] who found 151 ±10 //g h/ml. The relatively higher serum concentrations seen here for cefazolin are also reflected by comparisons made by a series of other investigations [5,7,10,16,17], The absolute levels of the various cephalosporins were usually, particularly for the first samples, higher in this study than in other studies [3,10,11,17], but of the same order as found for intravenous dosage by Kirby and Regamey [7], N icholas et al [12], and R attie and Ravin [13],…”

“…It is significant to note that the ratio ki2/k-2i is 1.0-1.8 for the two doses of cefazolin whereas all the other cephalosporins have values below 0.85 (table VII). Others [10,17], though, have found ki2/k2i ratios below 1.0 also for cefazolin. Whereas one of these studies [17] had ki2 values similar to the present one, the other had values of only 0.3 which is 7-8 times lower than that in this study and that in the study by S im on et al [17].…”

“…Although not identical concentrations in the tissues, in purulent foci like abscesses or empyemas or in fibrinous debries engulfing bacteria, serum levels being in balance with these subcompartments, are useful as monitors of the order of peripheral concentrations. Protein binding is a potential disadvantage for cefazolin with its protein binding of 84-86% [10], compared to 65% for cephalothin [10], 23-34% for cephacetril [13], and 40-50% for cephapirine [7]. The same is suggested by the findings of Bryant [4], and Simon et al [17] who examined concentrations in tissue fluids and noted approximately the same concentrations for cefazolin as for cephapirine although cefazolin had by far the higher serum concentrations (studied only for the first 2 h after a single dose).…”

Relationships between <i>in vitro</i> Susceptibility and Efficacy in Experimental Mouse Infection-Protection Assay of Cefazolin and Cephalothin using <i>Escherichia col</i><i>i</i> Strains

“…Although it is well known that different animal species may handle drugs in different ways, in the case of cefazolin the results ob tained in mouse are to be extrapolated to humans. On the basis of numer ous well-controlled clinical studies, cefazolin has been shown to have fa vorable and advantageous pharmacokinetic, pharmacodynamic, toxicol ogic and chemotherapeutic features in man [6,8,12,13].…”

“…It is a sta ble compound [8,15,26] and has a broad antibacterial spectrum with high degree of activity against both gram-negative and gram-positive bac teria. In separate studies, its in vitro activity and/or in vivo potency have been well established [1, 5, 8-12, 15, 17].…”