Stability of cephalosporins in commercial sera.
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Biomedical subjects
Publications and source records attributed to C H Nightingale.
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The cooperative development and initiation of a one-year pharmacy technician training program is described. The hospital's pharmacy and education departments formulated goals and objectives for the didactic and clinical areas of the program and developed methods to evaluate student competency and the program itself. The training for first class of students consisted of three months of didactic instruction, one month of laboratory experience, and eight months of on-the-job training. The program includes an observation of medication administration which is designed to increase the student's awareness of the entire medication process.
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In 24 patients undergoing open-heart operation, 2 gm of cefamandole was administered intravenously by bolus technique at various time intervals prior to operation. Samples of pericardial fluid, atrial appendage tissue, and serum were obtained simultaneously in order to compare antibiotic levels in these sites as a function of time. All samples were microbiologically assayed by disc diffusion. Using linear regression analysis, the atrial appendage and serum half-lives for cefamandole were 36 and 38 minutes, respectively. At 40 minutes, peak levels of cefamandole were observed both in pericardial fluid and in atrial appendage tissue. The peak concentrations of cefamandole were 50 micrograms/gm in atrial appendage and 25 micrograms/ml for free drug content in pericardial fluid. These amounts were appreciably above the mean minimum inhibitory concentration of cefamandole for penicillin-resistant staphylococci, the usual pathogens grown in infections following implant operation.
At various times before surgery, 33 patients undergoing coronary artery bypass or cardiac valve replacement surgery received a single 2.0-g dose of either cefazolin or cephradine. Simultaneous single serum, atrial appendage, and pericardial fluid samples were obtained from the patients at various times and analyzed for drug content. Compared with cephradine, cefazolin yielded higher total serum, atrial appendage, and pericardial fluid levels. Unbound (free) levels of cephradine in serum and pericardial fluid were, however, higher than those of cefazolin. It remains uncertain whether the higher and more prolonged total levels of cefazolin in the right atrial appendage and in serum, or the higher free levels of cephradine in pericardial fluid and in serum, provide either one with a therapeutic advantage.
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To prevent infection in 27 patients who underwent coronary artery bypass or cardiac valve replacement surgery, each patient received a single 2-g dose of either cephalothin or cephapirin intravenously before the operation (prior to opening of the chest cavity). Samples of the right atrial appendage, pericardial fluid, and serum were obtained at various intervals after injection of the antibiotic and were assayed for cephalosporin concentrations. Cephapirin consistently reached higher levels than cephalothin in the right atrial appendage and pericardial fluid; both cephalosporins, however, reach concentrations in these sites well above their minimal inhibitory concentrations (MICs) for penicillin-resistant staphylococci. Of particular interest was the brevity of the period (about 100 min) during which levels of both antibiotics were maintained above the MIC in the right atrial appendage. This finding emphasizes the need for administration of these antibiotics shortly before surgery.
Various cephalosporins with different degrees of protein binding were administered to human volunteers. Blood samples were collected as a function of time and were assayed for drug content by a microbiological assay. A pharmacokinetic analysis of the data was performed using a two-compartment model with and without protein binding in the central compartment and a perfusion model. Both the two-compartment model without protein binding and the physiological perfusion model adequately described the blood levels of all three cephalosporins.
A crossover experiment was utilized to compare the pharmacokinetics of a 1-g dose of cephalexin tablets, cephalexin capsules, or cephradine capsules in nine normal human volunteers. These antibiotics were administered as three formulations: two 500-mg capsulin every 6 hr for five doses, and one 1000-mg tablet of cephalexin every 6 hr for five doses. Pharmacokinetic parameters in the experimental groups showed no statistical differences (p greater than 0.1), indicating that these drugs are equivalent pharmacokinetically.
The antibiotic cephalexin was formulated as an oral prolonged-release tablet and evaluated by in vitro dissolution testing as well as in vivo in 10 human subjects. Comparisons were made of the time course of the blood levels among the prolonged-release formulation, the commercially available capsule, and intravenous administration. Even though lower peak blood levels were attained in the prolonged-release tablet, absorption continued for at least 6 hr. Comparison with in vitro dissolution data showed that absorption was dissolution rate limited. Bioavailability comparisons showed that the prolonged-release formulation was completely available, as was the commercial oral capsule.
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After 5 years of use, cefazolin can be considered similar to cephalothin as a therapeutic agent and in its potential for adverse reactions. When cefazolin and cephalothin are compared by appropriately designed clinical trials, neither cefazolin's slightly greater in-vitro susceptibility to staphylococcal beta-lactamase inactivation, nor its slightly greater microbiologic activity for some enterobacteraciae has been shown to result in any readily apparent therapeutic differences. The important differences between cefazolin and cephalothin--and this is also probably true with respect to cephapirin and cephradine--are not in therapeutic effectiveness, microbiologic activity, or toxicity but rather in pharmacokinetics and cost-effectiveness.
A rapid and sensitive fluorometric analysis for cephalosporins, which can also be applied to penicillins, is presented. The method involves reaction with 0.1 N sodium hydroxide at 100 degrees, producing stable fluorescent products. This method was applied to cephalexin and ampicillin with detection at concentrations as low as 0.01 mug/ml.
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The stability of aspirin in propoxyphene compound capsules made by three manufacturers, stored under a variety of temperature and humidity conditions, was compared. The cotton packing was removed from 100-capsule bottles, and the containers were stored (capped) under the following conditions: 25 c37 C and 50 C at both high (90%) and low (10%) humidity. No desiccant was removed from the bottles if originally present. The products tested were Darvon Compound-65 (two formulations) (Lilly), SK-65 Compound (Smith Kline & French) and Dolene Compound-65 (Lederle). Under all conditions, the stability of aspirin in the SK-65 Compound product was greater than that of Darvon Compound-65 which in turn was greater than Dolene Compound-65. Further, the rate of aspirin decomposition was greater in the latter product than in the others.
Preoperatively, to prevent infection, seventy-one patients who were to have total hip arthroplasty were given one gram of cephalothin, cephradine, or cefazolin intravenously. Simultaneous samples of bone and serum were obtained after various time intervals and assayed for cephalosporin concentration to correlate the antibiotic concentrations in these sites with time. Of the cephalosporins tested, cefazolin achieved the highest total peak levels in bone (thirty micrograms per gram), followed in descending order by cephradine (twenty-three micrograms per gram) and cephalothin (2.8 micrograms per gram). These peak levels in bone, reached twenty-five to forty minutes after injection, were sixty, 6.7, and fifteen times higher than the usual mean minimum inhibitory concentrations of cefazolin, cephradine, and cephalothin, respectively, for penicillin-resistant staphylococci. The half-lives of the antibiotics in bone were forty-two, forty, and thirty minutes, respectively.
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