Ceftezole, a new cephalosporin derivative, was compared with cefazolin, cephaloridine, and cephalothin. Data obtained indicate that it is a broad-spectrum antibiotic, with almost identical antimicrobial activity against pathogenic organisms isolated from patients. The therapeutic effect of ceftezole on experimental infections in mice was similar to that of cefazolin and was superior to that of cephalothin. The binding of ceftezole to serum proteins was somewhat less than that of cefazolin. The concentrations of ceftezole in the sera of test animals and human volunteers were determined after intramuscular injection of 20 mg/kg and after a single dose of 500 mg, respectively. The concentration of ceftezole in the serum of volunteers peaked at 24.9 mug/ml 15 min after injection and remained effective (about 2.6 mug/ml) at 4 h. The half-life in serum under the same conditions was 56 min, i.e., about one-half that of cefazolin. The 24-h urinary recovery rate was 87.5%. Most of the administered ceftezole was excreted unchanged mainly through the urinary tract. The biliary excretion rate in SD strain rats after intramuscular injection of 20 mg/kg was about 4.4%. As compared with commercially available cephalosporins, ceftezole was second only to cefazolin in biliary excretion rate. Various tissue levels of ceftezole in animals were higher than cephalothin but, with the exception of renal levels in the early stage after administration, were lower than cefazolin.

The pharmacokinetics offosmidomycin was investigated in animals and humans after parenteral and oral dosing. In dogs the serum concentration was 54.8 ,ug/ml at 0.25 h after an intravenous dose of 20 mg/kg, and the half-life was 1.14 h. Peak concentration was 41.4 ;ig/ml after an intramuscular dose of 20 mg/kg and 16.6 ,g/ ml after an oral dose of 40 mg/kg. In volunteers, the serum concentration 0.25 h after dosing was 157 jig/ml after an intravenous dose of 30 mg/kg, 12.3 ,ug/ml after an intramuscular dose of 7.5 mg/kg, and 2.45 j,g/ml after an oral dose of 500 mg. More than 90% of the given dose was excreted in the 24-h urine in rats and dogs after parenteral dosing with 20 mg/kg. The 24-h urinary recovery was 45.8% of the given dose in rats after oral dosing with 100 mg/kg and 37.8% in dogs after oral dosing with 40 mg/kg. In volunteers 85.5% of the intravenous dose (30 mg/kg), 66.4% of the intramuscular dose (7.5 mg/kg), and 26.0% of the oral dose (500 mg) were excreted unchanged in the 24-h urine. In the multiple-dose study, there was no accumulation of fosmidomycin in the serum even after 21 consecutive intramuscular dosings of 1 g every 6 h or 29 consecutive 0.5-h drip infusions of 2 g every 6 h. Biliary excretion was extremely low in rats. Fosmidomycin was well distributed to the tissues of rats after parenteral and oral dosing. The lymph concentrations in dogs were nearly the same as serum concentrations. Serum protein binding was low (4% or less) to mouse, rat, dog, and human serum.

The pharmacokinetic profile of ceftizoxime was studied in mice, rats, dogs, and monkeys given the drug in a single parenteral dose. The serum data after an intravenous injection were analyzed by the two-compartment open model. Cefotiam, cefmetazole, cefotaxime, and cefamandole were used as reference drugs. High concentrations of ceftizoxime were attained in the sera of all test animals and in the tissues of rats after parenteral dosing. The serum concentrations of ceftizoxime were higher than those of the other antibiotics in large animals (dogs and monkeys), but were lower in small animals (mice and rats). About 80% of ceftizoxime was excreted unchanged in the 24-h urine of all species tested. The biliary excretion of ceftizoxime was low: 3.7% in rats and 0.59% in dogs. However, therapeutically significant concentrations of ceftizoxime were found in the bile of dogs. Ceftizoxime was stable in biological fluids such as serum, urine, and tissue homogenates, but cefotaxime was unstable in rat tissue homogenates. Binding of ceftizoxime to serum protein in all species was the lowest of all the antibiotics: 31% for humans, 17% for dogs, and 32% for rats.Ceftizoxime, a new parenteral cephalosporin derivative, is more active against various gramnegative bacilli, including the opportunistic pathogens such as Enterobacter, Citrobacter spp., and Serratia marcescens, than such cephalosporins as cefotiam, cefuroxime, cefotaxime, and cefmetazole (5). In the present study the pharmacokinetics, metabolism in animals, binding to serum protein, and stability of ceftizoxime were evaluated. Cefotiam, cefamandole, cefotaxime, and cefinetazole, all recently developed cephalosporins, were used as reference drugs.MATERIALS AND METHODSAntibiotics. The compounds used in this study included ceftizoxime (FK 749, Fujisawa, Japan), cefotiam (SCE 963, Takeda, Japan), cefamandole (Eli IJlly & Co., Indianapolis, Ind.), cefmetazole (CS 1170, Sankyo, Japan), and cefotaxime (HR 756, HoechstRoussel, West Germany).Animals. The animals used in this study included 6-week-old male JCL:ICR strain mice, 6-week-old male JCL:SD strain rats, 7.5-to 15.0-kg male beagle dogs, and 5.8-to 9.1-kg male rhesus monkeys. Dosing. The antibiotics for injection were dissolved in 0.9% saline. The drugs were given in a dose of 20 mg/kg to all test animals. The volumes were: 0.25 ml per animal by the intravenous (i.v.) and subcutaneous routes to mice; 5 ml/kg of body weight by the intramuscular (i.m.) and i.v. routes to rats; and 0.5 ml/kg of body weight by the i.m. and i.v. routes to dogs and monkeys.Serum sampling. Blood samples were collected: (i) from the carotid artery of mice at specified intervals after injection; (ii) by heart puncture from rats; (iii) from the antecubital veins of dogs and monkeys. The antibiotic concentrations in the serum were bioassayed using standard solutions prepared with control serum of the respective species of animals.Pharmacokinetic analysis. The serum concentration-time data were fitted to a two-compartment open model (4) using Marqu...

The protective effect of an immunoactive peptide, D-lactoyl-L-alanyl-r-D-glutamyl-(L)meso-diaminopimelyl-(L)-glycine (FK-156) and a related compound, heptanoyl-r-D-glutamyl-(L)meso-diaminopimelyl-(D)-alanine (FK-565) was determined in mice with various kinds of microbial infections. FK-156 and FK-565 were given to mice either subcutaneously or orally before challenge. The drugs enhanced significantly the defense of mice against acute systemic infections induced by various extracellular and facultative intracellular organisms, and subcutaneous abscess by Staphylococcus aureus. The protective effect of these drugs against Escherichia coli infection differed considerably depending on the route of administration; FK-156 was only effective by the parenteral route; however, FK-565 was effective by both parenteral and oral routes. After subcutaneous dosing with FK-156, the enhancement of host defense of mice against E. coli infection was more rapid than against Listeria infection. The enhancing effects of FK-156 and FK-565 on host defense of mice against pseudomonal infection was more potent than other immunoactive drugs.

No abstract