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At least 19 recordsLinked to original sources
PubMed1968

In vitro antimicrobial activity and human pharmacology of cephaloglycin.

Serum and urine concentrations of cephaloglycin (an orally absorbed derivative of cephalosporin C) were determined in normal volunteers and in patients. The in vitro activity of cephaloglycin was also studied. All strains of group A streptococci (Streptococcus pyogenes) and Diplococcus pneumoniae were inhibited by 0.4 mug of cephaloglycin per ml. Eighty per cent of the Staphylococcus aureus strains and about 50% of the Escherichia coli and Proteus mirabilis strains were inhibited by 1.6 mug of cephaloglycin per ml. Klebsiella-Aerobacter species were more resistant to cephaloglycin and 12.5 mug per ml was required to inhibit 70% of these strains. When single doses of 250, 500, or 1,000 mg of cephaloglycin were administered to fasting volunteers, a peak serum concentration of at least 0.5 mug per ml was achieved. A full breakfast did not interfere with absorption of cephaloglycin. Probenecid enhanced both the peak serum concentration and the duration of antibiotic activity in the serum. Serum concentrations of cephaloglycin were even higher in patients who were receiving repeated doses. The peak serum concentrations of cephaloglycin in all volunteers and patients were adequate to inhibit all strains of group A streptococci and D. pneumoniae. Many of the peak serum concentrations were adequate to inhibit some strains of S. aureus, E. coli, and P. mirabilis. Urine levels of cephaloglycin were high enough in all volunteers and patients to inhibit more than 90% of the E. coli and P. mirabilis strains and over 70% of the strains of Klebsiella-Aerobacter.

Bacteria↗
PubMed1989

Oxidative and mitochondrial toxic effects of cephalosporin antibiotics in the kidney. A comparative study of cephaloridine and cephaloglycin.

Cephaloridine and cephaloglycin are the two most nephrotoxic cephalosporins released for human use. Cephaloridine has been shown to produce both oxidative and mitochondrial respiratory injury in renal cortex in patterns of dose (or concentration) and time that are consistent with pathogenicity. Cephaloglycin also produces respiratory toxicity, and recent studies have provided evidence that this injury results from an inactivation of mitochondrial anionic substrate transporters. The abilities of cephaloglycin to produce oxidative changes and cephaloridine to block mitochondrial substrate uptake have not been examined yet. We therefore compared these two cephalosporins with one another and with cephalexin, which is not nephrotoxic, in the production of the following: (1) several components of oxidative stress or damage [depletion of reduced glutathione (GSH) and production of oxidized glutathione (GSSG) in renal cortex, inhibition of glutathione reductase in vitro, and production of the lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CDs) in renal cortex]; and (2) renal cortical mitochondrial toxicity [to both respiration with, and the transport of, succinate]. Cephaloridine depleted GSH and elevated GSSG in renal cortex, inhibited glutathione reductase, and increased both MDA in whole cortex and CDs in cortical microsomes and mitochondria. While cephaloglycin depleted GSH at least as much as did cephaloridine, it produced one-fifth as much GSSG and had little or no effect on glutathione reductase activity or on cortical MDA or microsomal CDs; cephaloglycin caused a transient small increase of mitochondrial CDs. Cephalexin produced no oxidative changes except for a slight increase of mitochondrial CDs comparable to that produced by cephaloglycin. Both cephaloridine and cephaloglycin, but not cephalexin, decreased the unidirectional uptake of, and respiration with, succinate in cortical mitochondria. We conclude that cephaloridine and cephaloglycin are both toxic to mitochondrial substrate uptake and respiration, but differ significantly in their generation of products of oxidation.

Animals↗
PubMed1980

Cephalosporin nephrotoxicity. Transport, cytotoxicity and mitochondrial toxicity of cephaloglycin.

The cephalosporin antibiotics are secreted by the renal organic anion transport system. Several of them, including cephaloridine and caphaloglycin, produce a proximal renal tubular necrosis which can be prevented by inhibitors of organic anion transport. Although cephaloridine is actively transported into the tubular cell at the antiluminal side like other cephalosporins, it undergoes a limited rate of subsequent movement across the luminal membrane into the tubular fluid. The very high intracellular concentrations that result from this unusual process are believed to contribute to the significant toxicity of cephaloridine. Cephaloglycin is at least as toxic, but is secreted more normally across the proximal tubular cell. For this reason, studies were undertaken to evaluate the cytotoxicity, cortical concentrations and mitochondrial respiratory toxicity of this cephalosporin in the rabbit kidney. A dose of 100 mg/kg of caphaloglycin produces as much damage as does 150 mg/kg of cephaloridine. The steady-state cortex-to-serum concentration ratio of cephaloglycin, 5.6 +/- 0.8 S.E. (n = 5), is significantly lower (P < .001) than the corresponding measurement for cephaloridine, 121.9 +/- 1.2 (n = 7), and is not significantly different from that of p-aminohippurate. In further contrast to cephaloridine, the cortical concentration of cephaloglycin declines substantially, from 930 +/- 112 (n = 5) to 297 +/- 46 (n = 5) micrograms/g of wet tissue, over the first hour after cessation of infusion (P < .001) and is essentially unmeasurable by 2 hr. The fact that there is not the prolonged intracellular trapping of cephaloglycin that is seen with cephaloridine leads to the conclusion that the former must either bind more strongly to its target receptor or produce a more irreversible insult than does the latter cephalosporin. Several lines of evidence are presented which support this hypothesis. The most important of these are that cephaloglycin is cumulatively nephrotoxic, whereas cephaloridine is not, and that the in vivo toxicity of cephaloglycin to cortical mitochondria, unlike that of cephaloridine, is not significantly diminished by the mitochondrial isolation process. This very early in vivo respiratory toxicity of cephaloglycin and the lack of significant similar toxicity of cephalexin provide new evidence that the effect on mitochondria may have a pathogenic role in cephalosporin nephrotoxicity.

Animals↗
PubMed1968

Cephalexin and cephaloglycin activity in vitro and absorption and urinary excretion of single oral doses in normal young adults.

A large number of recently isolated bacterial pathogens were tested for susceptibility to cephalexin and cephaloglycin by the replica inoculating method. Strains of group A hemolytic streptococci, viridans (alpha and gamma) streptococci, pneumococci, gonococci, meningococci, and penicillin G-sensitive Staphylococcus aureus were all moderately to highly susceptible to both of these cephalosporin analogues, nearly all of the strains being two to eight (median four) times more susceptible to cephaloglycin than to cephalexin. The penicillin G-resistant, penicillinase-producing strains of S. aureus varied in their susceptibility; many were moderately resistant to both analogues, particularly to cephalexin. Strains of enterococci, Haemophilus influenzae, and most of the common gram-negative bacilli were moderately to highly resistant. Reducing the size of the inoculum had variable effects on inhibition by these drugs, depending on the species or strain. The activity of cephalexin was very little affected by pH of the medium within the clinical range or by incubation at 37 C in broth for up to 24 hr. In contrast, cephaloglycin in broth deteriorated rapidly at 37 C, and its activity was markedly reduced in alkaline medium. Both cephalexin and cephaloglycin were rapidly absorbed and excreted into the urine after single oral doses of 500 mg. Much higher levels were achieved and sustained with the former. Absorption of both analogues was delayed when taken with food, and the levels in the serum were significantly higher and better sustained when probenecid was also given. Very high concentrations of cephalexin were excreted into the urine during the first 4 hr, and the levels were still high in the 4- to 8-hr collection. The concentrations of cephaloglycin in the urine at these times were much lower. An average of 80 to 93% of the dose of cephalexin and 25 to 30% of the cephaloglycin were accounted for as active drug in the urine collected in 8 hr. Both analogues were well tolerated.

Adult↗
PubMed1980

Chromatographic analysis and pharmacokinetic investigation of cephaloglycin and its metabolites in man.

Metabolism and pharmacokinetics of cephaloglycin in man were investigated. High performance liquid chromatographic and gas chromatographic-mass spectrometric analyses of metabolites excreted in human urine following oral administration of cephaloglycin revealed that cephaloglycin was biotransformed in two pathways i.e. elimination of 3-acetyl group and hydrolysis of side chain amide linkage. The former yielded deacetylcephaloglycin, a part of which further underwent lactonization to deacetylcephaloglycin lactone, and the latter led to benzoyl formic acid via phenylglycine. The urinary excretion amounts of these metabolites and intact cephaloglycin were determined by a reversed phase ion pair high performance liquid chromatography. The average total excretion amounts at infinite time accounted for 0.50% of the administered dose for intact cephaloglycin, 17.09% for deacetylcephaloglycin, 0.35% for deacetylcephaloglycin lactone, and 0.86% for benzoyl formic acid. The excretion of phenylglycine was less than 0.2%, its chromatographic peak being too small to allow accurate determination. The rate constants for absorption, metabolism, and urinary excretion were estimated by the moment analysis of the excretion rate-time curves.

Adult↗
PubMed1990

The renal mitochondrial toxicity of beta-lactam antibiotics: in vitro effects of cephaloglycin and imipenem.

The nephrotoxic beta-lactam antibiotics cephaloridine, cephaloglycin, and imipenem produce irreversible injury to renal mitochondrial anionic substrate uptake and respiration after 1 to 2 h of in vivo exposure. Toxicity during in vitro exposure is nearly identical but is immediate in onset and is reversed by the mitochondria being washed or the substrate concentrations being increased. A model of injury that accounts for these findings proposes that the beta-lactams fit carriers for mitochondrial substrate uptake, causing inhibition that is initially reversible and becomes irreversible as the antibiotics acylate the transporters. These studies were designed to create an environment of prolonged in vitro exposure, first, to determine whether toxicity becomes irreversible with time and, second, to study the molecular properties of toxicity. Respiration with and the uptake of succinate and ADP were measured in rabbit renal cortical mitochondria exposed for 2 to 6 h to 300 to 3,000 micrograms of cephalexin (nontoxic) or cephaloglycin or imipenem (nephrotoxic) per mL and then washed to remove the antibiotic. In vitro cephalexin reduced respiration only slightly and was therefore not studied further. Cephaloglycin and imipenem irreversibly reduced both respiration and succinate uptake. ADP uptake was unaffected by cephaloglycin and was slightly reduced by imipenem. Finally, cilastatin, which prevents the tubular necrosis produced by imipenem in vivo, reduced its mitochondrial toxicity in vitro. It is concluded that the pattern of in vitro injury of the nephrotoxic beta-lactams to mitochondrial substrate uptake and respiration evolves in a time-dependent and concentration-dependent manner, consistent with the proposed model of acylation and inactivation of substrate transporters, and that the protective action of cilastatin against imipenem occurs at least partly at a subcellular level.

Adenosine Diphosphate↗
PubMed1979

Acidic degredation of cephaloglycin and high performance liquid chromatographic determination of deacetylcephaloglycin in human urine.

In order to provide fundamental knowledge about the determination of deacetylcephaloglycin excreted in human urine as an active metabolite of cephaloglycin, the degradation of cephaloglycin in acidic media has been investigated with varying reaction temperature between 30 degrees and 50 degrees C and pH between 1.2 and 2.8. The degradation pathway observed under these conditions was the elimination of the 3-acetyl group yielding deacetylcephaloglycin followed by formation of deacetylcephaloglycin lactone. Estimation of first order rate constants revealed that deacetylation is the rate-determining step for the degradation of cephaloglycin to the lactone. It is found from the kinetic results that reproducible assays of deacetylcephaloglycin excreted in urine can be achieved by a quantitative conversion to deacetylcephaloglycin lactone in a medium of pH 1.4 at 37 degrees C for 2 hours, followed by a reversed-phase ion-pair high-performance liquid chromatography. The utility of the present method is demonstrated by determining the time course of urinary excretion of deacetylcephaloglycin after oral administration of cephaloglycin capsule.

Acids↗
PubMed1971

Cephaloglycin and its biologically active metabolite desacetylcephaloglycin.

Chromatographic studies and microbiological assays show that, after oral administration, cephaloglycin is partially converted in man to a biologically active metabolite desacetylcephaloglycin. The antibacterial activity of this metabolite compared to that of cephaloglycin is equivalent against gram-positive organisms but is lower against gram-negative bacilli. Successful therapy of urinary tract infections with cephaloglycin must be mainly attributed to the antibacterial activity of this metabolite. At the present time, it is not possible to assess what influence low amounts of unaltered cephaloglycin have on the outcome of therapy.

Administration, Oral↗
PubMed1965

IN VITRO AND IN VIVO LABORATORY EVALUATION OF CEPHALOGLYCIN AND CEPHALORIDINE.

Two new antibiotics, structurally related to cephalothin, have been given the generic names cephaloglycin and cephaloridine. Cephaloglycin is the dipolar ion of 7-(d-alpha-aminophenylacetamido)-cephalosporanic acid. Cephaloridine is 7-[alpha-(2-thiophene)acetamido]-3-(1-pyridylmethyl)-3-cephem-4-carboxylic acid betaine. These new compounds were evaluated simultaneously. The broad spectrum of activity observed in vitro and in vivo with both antibiotics, the good oral absorption obtained with cephaloglycin, and the stability of cephaloridine are emphasized. The data suggest that both antibiotics merit clinical trial in humans.

Alcaligenes↗
PubMed1990

Effect of cefatrizine and cephaloglycine on L-leucine absorption in rat jejunum.

1. The oral cephalosporins: cefatrizine and cephaloglycine inhibit the L-leucine absorption in vivo on rat jejunum. 2. This inhibition is dose and time dependent and the effect is irreversible. 3. These antibiotics have a systemic effect on L-leucine absorption. 4. The inhibition of these antibiotics affect only leucine transport, without affecting the diffusion. 5. Cefatrizine and cephaloglycine inhibit the basolateral (Na(+)-K+) ATPase activity in rat jejunum.

Animals↗
PubMed1977

Cephalosporins. I. Cephaloglycin analogs with six-membered heterocycles in the C-3 side chain.

Cephaloglycin analogs with six-membered heterocycles in the C-3 side chain have been prepared by nucleophilic substitution of 7-aminocephalosporanic acid with appropriate azine thiols followed by 7-N-acylation with phenylglycine by the mixed anhydride method. Seventeen thiols of non-substituted or substituted pyridines, pyridazines, pyrimidines, pyrazines and triazines were used as the S-nucleophiles. In general, pyridazine thiols gave cephalosporins processing good antimicrobial activity against both gram-positive and gram-negative bacteria. Among them 6-hydroxypyridazine-3-thiol gave the most active compound of this series, BB-S 118 (1f), which was significantly more active than cephalexin and cephaloglycin in vitro against gram-positive and gram negative bacteria.

Animals↗
PubMed1977

Fluorimetric assay of cephradine, cephalexin and cephaloglycin.

1 A simple, rapid and reproducible fluorimetric assay for cephradine, cephalexin and cephaloglycin is described. 2 The method involves addition of formaldehyde which catalyses the formation of fluorescent derivatives. 3 The structural similarities between the side chains of these antibiotics and their identical excitation and emission spectra suggest that they may be forming similar fluorescent derivatives.

Cephalexin↗