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Pharmacokinetic interpretation of cephradine levels in serum after intravenous and extravascular administration in humans.

Pharmacokinetic parameters were calculated from intravenous data based upon a two-compartment open model. These parameters were subsequently used to determine the absorption rates and bioavailability of cephradine administered intramuscularly and orally. The results indicate that cephradine obeys dose-independent kinetics and that biological availability is complete from all dosage forms.

Administration, Oral↗

Comparative human oral clinical pharmacology of cefadroxil, cephalexin, and cephradine.

At equivalent oral doses, cefadroxil has a longer serum half-life, slower urinary excretion rate, greater area under the serum level versus time curve than cephalexin or cephradine, and peak serum concentrations that are 75 to 80% those of cephalexin. The calculated, apparent in vivo volume of distribution of cefadroxil is greater than that of cephalexin. These properties infer greater persistence of cefadroxil in serum and urine and more prolonged in vivo bacterial exposure to cefadroxil than to cephalexin or cephradine. Neither cefadroxil nor cephalexin demonstrates drug accumulation on repeated administration. The serum levels achieved by cefadroxil are unaffected by food. The pharmacokinetic properties of cefadroxil are supportive of the development of clinical efficacy data which could indicate that cefadroxil could be administered at 12-h intervals.

Adult↗

Comparison of in vitro activity of cephalexin, cephradine, and cefaclor.

Inhibitory activity of cephalexin, cephradine, and cefaclor was compared by the WHO-ICS agar dilution technique. Cefaclor was substantially more active against staphylococci, streptococci, gonococci, meningococci, Haemophilus, Escherichia coli, Klebsiella pneumoniae, Citrobacter diversus, Proteus mirabilis, salmonellae, and shigellae than was cephalexin, which in turn was more active than cephradine. Cefaclor appeared to be less resistant to staphylococcal penicillinase than did the other two agents. None of these cephalosporins was active against Enterobacter, Serratia, indole-positive Proteeae, Pseudomonas, or Bacteroides fragilis.

Bacteroides↗

In vitro susceptibility of Haemophilus influenzae to sulfamethoxazole-trimethoprim and cefaclor, cephalexin, and cephradine.

Sulfamethoxazole-trimethoprim and three oral cephalosporins, cefaclor, cephalexin, and cephradine, were evaluated in vitro as possible alternatives to chloramphenicol in the treatment of non-central nervous system infections due to ampicillin-resistant Haemophilus influenzae. Sixty-four isolates of H. influenzae, including 31 beta-lactamase-positive strains, were tested by the agar dilution method. All strains were inhibited by 0.78/0.039 mug sulfamethoxazole-trimethoprim per ml and by 0.78 mug of chloramphenicol per ml. At 6.25 mug/ml, 100, 11, and 3% of all strains were inhibited by cefaclor, cephalexin, and cephradine, respectively. Thus, on the basis of drug concentrations presumably achievable in serum, 100% of strains were susceptible to sulfamethoxazole-trimethoprim, chloramphenicol, and cefaclor. However, a considerable inoculum effect was noted with both beta-lactamase-positive and -negative strains, when tested with sulfamethoxazole-trimethoprim; the minimal inhibitory concentrations of cefaclor were only slightly affected. Also, synergistic effects of sulfamethoxazole-trimethoprim, sulfamethoxazole-erythromycin, and sulfamethoxazole-cefaclor were seen when combinations were tested against both beta-lactamase-positive and -negative strains, as determined by minimal inhibitory concentrations measured by the broth dilution method and by killing curve analyses. These results support further evaluation of these combinations and of cefaclor alone for the treatment of non-central nervous system infections due to H. influenzae.

Cephalosporins↗

Susceptibility of Gardnerella vaginalis to cephradine.

The activity of cephradine and the influence of pH on its activity against 70 Gardnerella vaginalis strains were determined. Serial dilutions of cephradine (0.062 to 256 micrograms/ml) were incorporated into Dunkelberg agar, inoculated with a Steers replicator, incubated in 5% CO2 for 48 h, and examined. The minimal inhibitory concentrations for 90% of the isolates were 16 and 8.0 micrograms/ml at pH 7.0 to 6.0 and 5.5, respectively.

Cephalosporins↗

Effect of amoxicillin-clavulanate and cephradine on the fecal flora of healthy volunteers not exposed to a hospital environment.

A 7-day course of either cephradine or amoxicillin-clavulanate treatment caused no significant change in fecal flora composition, except that staphylococci were virtually eliminated in both groups. Some amoxicillin-resistant coliforms were isolated after treatment in both groups, but cephradine- or amoxicillin-clavulanate-resistant coliforms were rarely isolated.

Amoxicillin↗

Use of polyvinylpyrrolidone in the testing of staphylococci for sensitivity to methicillin and cephradine.

The use of polyvinylpyrrolidone, an inert polymer resembling plasma proteins in its colligative effects, in the testing of micrococcaceae for sensitivity to methicillin and cephradine is described. Generally results are quite comparable with those of conventional methods. The absence of any inhibitory effect of the polymer compared to sodium chloride, and its physiological inertia compared to sucrose, along with its suitability for sterilisation by autoclaving are seen as advantages. It is suggested that the use of this substance may give results which are more applicable to the in vivo situation. This may apply particularly in the case of cephradine.

Cephalosporins↗

Effects of test conditions on the susceptibility of staphylococci in vitro to cephradine, cephaloridine, cephalexin, and cefuroxime.

Methicillin-resistant staphylococci were tested for susceptibility to cephradine, cephaloridine, cephalexin, and cefuroxime and 30 degree C and 37 degree C on ordinary media and on media of enhanced osmotic strength. The coagulase-negative strains were divided into Staphylococcus epidermis and Staphylococcus hominis. Generally the number of susceptible strains decreased with low incubation temperature and osmotic support. When Staphylococcus aureus was tested against cephalexin and cefuroxime, most were susceptible at 37 degree C whereas all were resistant at 30 degree C. A similar trend was found in the case of cephradine, where it was accentuated by osmotic support. While almost all strains of Staph. epidermidis were sensitive to all four drugs under all test conditions, the susceptibility of Staph. hominis was generally decreased by either lower incubation temperature or osmotic support or both.

Cefuroxime↗

Biophotometric comparison of cephalexin and cephradine against gram-positive bacteria.

We have compared the antibacterial activities of cephalexin and cephradine against Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus (Micrococcus spp. type III), and group B streptococci (35 strains in total), using the Biophotometer. Analysis of growth curves obtained in the presence of various concentrations of the antibiotics revealed little difference between the activities of the two cephalosporins. However, both antibiotics showed maximal activity at 8-16 microgram/ml, and increasing the concentration past this point resulted in a reduced antibacterial effect. Unlike the other species tested, streptococci were not lysed by cephalexin or cephradine.

Cephalexin↗

Comparative efficacy and safety of cephradine and cephalexin in children.

Cephradine was compared to cephalexin a randomized, double-blind study for the treatment of bacterial infections in 162 children between four months and eleven years of age. In addition to evaluations of clinical and bacteriologic responses to therapy, the relative safety of the two cephalosporins was assessed for all children, including eight who were not included in the evaluation of drug efficacy. The children in the efficacy evaluation had either lobar pneumonia or skin infections and received oral suspensions of cephradine (25-110 mg/kg per day) or cephalexin (25-150 mg/kg per day) for five to fifteen days. Overall clinical and bacteriologic responses were nearly identical in the two groups, and both antibiotics proved to equally safe and effective for use paediatric practice.

Cephalexin↗

Recurrence of otitis media after antibiotic therapy: comparison of cephradine and amoxycillin.

The long-term effectiveness of cephradine and amoxycillin in the treatment of otitis media was evaluated in one hundred children ranging in age from 4 months to 14 years. The immediate clinical response was comparable in both treatment groups, but the recurrence rate during a 12-month follow-up period was considerably lower in the patients treated with cephradine. The incidence of side-effects was similar in the two groups.

Adolescent↗

Cephradine in urinary tract infections: a double-blind comparison with ampicillin.

A double-blind trial was carried out comparing cephradine and ampicillin in the treatment of urinary tract infections in 42 females attending a hospital Department of Obstetrics and Gynaecology. Results showed that patients did better in the cephradine group than the ampicillin group, both bacteriologically and clinically. The numbers in each group were small, however, and did not reach statistical significance.

Adolescent↗

A study on tissue concentrations of cephradine achieved in patients with peripheral vascular disease.

The levels of cephradine were measured in serum, voluntary muscle and subcutaneous fat samples collected from 30 patients during surgical operations for peripheral vascular disease. Cephradine 2 g was administered in two equal doses by intramuscular and intravenous routes before each operation. The mean levels found in the serum and muscle were well above the minimum inhibitory concentrations required for most important Gram-positive and Gram-negative pathogens, in contrast to the relatively low mean level found in subcutaneous fat.

Adipose Tissue↗

The determination of cephradine and cephalexin by reverse phase high-performance liquid chromatography.

The application of reverse phase high-performance liquid chromatography to the separation and analysis of cephradine and cephalexin is demonstrated. The procedure has been applied to chemicals, pharmaceutical formulations and reaction solutions. The preparation of samples is simple and rapid. Chromatographic conditions are described for both pellicular and small particle columns. The feasibility of determing cephradine and cephalexin in physiological fluids has also been demonstrated.

Capsules↗

Bactericidal activity of cefadroxil, cephalexin, and cephradine in an in vitro pharmacokinetic model.

Cefadroxil (Duricef, Mead Johnson and Company), resembles cephalexin and cephradine in spectrum of antibacterial activity but differs in human pharmacokinetic properties. Whether the latter are likely to affect activity in vivo was assessed by determining bactericidal activity against clinical isolates under conditions simulating the variation of drug concentration in the blood stream after an oral dose of 500 mg to adults. In this kinetic model, cefadroxil was more active than cephalexin or cephradine against Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae and one of two strains of Escherichia coli. The other strain of E. coli was virtually unaffected by the cephalosporins. S. pyogenes was equally susceptible to all three cephalosporins. Analysis of the results suggest that the pharmocokinetic properties of an antibiotic affect its activity in the blood stream, provided the susceptibility of the infecting organism is concentration-dependent within the range of drug concentration occurring in serum.

Adult↗

[Administration of cephradine to dermatoses by injection (author's transl)].

Ten cases of various kinds of dermatoses underwent cephradine by injection. Two cases injected cephradine intramuscularly resulted in severe pain. Three of 4 cases with pyogenic skin infection revealed excellent results. Three cases were prevented from secondary infection. Adverse effects such as vertigo were avoided by lowering the speed of intravenous injection. No abnormal findings of serum GOT and GPT levels after the completion of the treatment was noted in 7 of 8 cases, but one case which was administrated large dosis of corticosteroid concomitantly revealed elevated level in this finding.

Adult↗

A preliminary report on cephradine.

Plasma cephradine levels were measured after parenteral and oral administration to healthy adults. Plasma cephradine contrations of 7 - 15 mug/ml were measured after 0.5 g had been administered by mouth, and concentrations of 12 - 57 mug/ml were measured after parenteral administration; they fell to 3 mug/ml within 240 minutes except after intramuscular administration. The results of an open clinical trial conducted among 10 patients suffering from urinary tract infections were satisfactory.

Administration, Oral↗

Comparative efficacy and tolerability of cephradine and cefuroxime axetil in the treatment of acute dysuria and/or frequency in general practice.

One hundred and thirteen patients with dysuria and/or frequency were treated randomly with either 500 mg cephradine 12-hourly or 125 mg cefuroxime axetil 12-hourly, for seven days. A total of 71 patients were found to have urinary infection: bacteriological cure rates were 97% one week post-treatment, and 96% five weeks post-treatment, for both antibiotics. On direct questioning, adverse events were reported by eight patients out of 59 taking cephradine and by three of 54 who had received cefuroxime axetil. However, only three and one respectively stopped taking the antibiotic due to the adverse event. Analysis of diary cards, completed by 109 patients, showed a significantly higher incidence of increased frequency of bowel movements in those taking cefuroxime axetil. It is concluded that both antibiotics are of equal value in the treatment of simple acute urinary infections in general practice.

Adolescent↗