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Biomedical subjects

D G Fraser

Publications and source records attributed to D G Fraser.

At least 37 records · Page 2Linked to original sources
PubMed1980

Displacement of phenytoin from plasma binding sites by salicylate.

Six healthy male subjects received phenytoin sodium as 9 100-mg capsules alone or with aspirin in a randomized, crossover fashion. Aspirin, 975 mg every 6 hr, was started 22 hr before a phenytoin dose and continued for an additional 48 hr during blood sampling. Mean 4-hr plasma salicylate levels ranged from 104 to 157 micrograms/ml during the sampling period. Individual mean values for the free fraction of salicylate varied from 0.107 to 0.167. The fraction of free phenytoin in plasma rose from 0.128 +/- 0.004 to 0.163 +/- 0.009 when aspirin was given (p less than 0.001). Subjects had lower total phenytoin 48-hr area under the curve (AUC) values when on aspirin (323 +/- 36 without and 261 +/- 49 micrograms . hr . ml-1 with aspirin; p less than 0.001) but free phenytoin AUC values were unchanged (41.4 +/- 4.5 and 42.4 +/- 9.0 micrograms . hr . ml-1; p less than 0.5). Thus, more rapid clearance of total phenytoin probably compensated for salicylate displacement of phenytoin from plasma protein binding sites. Total phenytoin levels for therapeutic monitoring must be interpreted cautiously when patients also receive salicylate.

Adult↗
PubMed1980

Selection of an oral erythromycin product.

The chemistry, bioavailability, and adverse effects of erythromycin base, stearate, estolate, and ethylsuccinate are reviewed. Criteria for the evaluation of erythromycin bioavailability studies include study design, patient population, meal composition and timing, and assay methodology. Based on these criteria, the bioavailability of individual erythromycin products are evaluated in this paper. Compared with other antibiotics, the erythromycins have a good safety record. However, both the estolate and ethylsuccinate forms of erythromycin may cause hepatotoxity. Considering bioavailability and adverse effect data, a specific brand of enteric-coated erythromycin base tablets is recommended for erythromycin-sensitive infections in adults. For pediatric patients, a liquid formulation of erythromycin estolate or erythromycin ethylsuccinate is recommended.

Administration, Oral↗
PubMed1980

Phenytoin toxicity and blood levels after a large oral dose.

The pharmacokinetics and side effects of a single oral 900-mg dose of phenytoin sodium were studied in six healthy men. Nine 100-mg phenytoin sodium capsules were administered with water to six fasting healthy men. Phenytoin plasma levels were measured by gas chromatography for up to 48 hours after dosing. Patients were observed and tested for gastrointestinal, cardiovascular, and neurologic side effects. Peak total (bound and free) plasma phenytoin levels were within the therapeutic range (10--20 microgram/ml) for two subjects and close (not less than 8.39 microgram/ml) for the remaining four. Peak free drug levels were 1.01--1.60 microgram/ml. Time to reach total and free peak plasma levels was long and variable (6--14 hours and 2--10 hours, respectively). Phenytoin protein binding (11.9--13.6%) was relatively stable among patients and at various plasma levels. A few mild transient side effects were noted; most occurred within two to four hours after dosing. Sinus bradycardia and a shortened PR interval were noted in two patients but did not correlate with peak plasma phenytoin levels. It appears that an oral loading dose of phenytoin sodium may be useful in ambulatory patients but further study of its side effects is recommended.

Adult↗
PubMed1979

Autoimmune myocarditis: a clinical entity.

In a case of myocarditis electron microscopic and immunoflourescent studies of a transmural myocardial biopsy specimen indicated an autoimmune process. Extensive inflammatory cell infiltration, immunoglobulin and complement deposition along the sarcolemma and in the interstitium, and capillary endothelial injury were found. After a short course of immunosuppressive therapy the inflammatory process was replaced by collagenous scarring and lymphocytic depletion; the blood vessels were then normal. Earlier therapy in such cases may be lifesaving.

Adult↗
PubMedDate not supplied

Cinoxacin: mechanism of action, spectrum of activity, pharmacokinetics, adverse reactions, and therapeutic indications.

Cinoxacin, a chemotherapeutic agent that inhibits bacterial DNA synthesis, has recently been approved for the treatment of initial and recurrent bacterial urinary tract infections. Although closely related to nalidixic acid, cinoxacin possesses some distinct characteristics: rapid attainment of therapeutic urinary concentrations and greater activity against strains of Enterobacteriaceae that cause urinary tract infections. Biopharmaceutical properties include serum protein binding of approximately 70%, 50-60% excretion of intact drug in the urine of patients with normal renal function, and an elimination half-life of approximately one hour. The elimination half-life is increased in patients with decreased renal function and when probenecid is coadministered. Adverse events occur infrequently and consist of nausea, vomiting, headache, dizziness, and hypersensitivity reactions. The drug compares favorably with standard therapies for the treatment of bacterial cystitis and recurrent urinary tract infections. Initial studies demonstrate that cinoxacin has substantial efficacy as a prophylactic agent for those women who experience recurrent, symptomatic urinary tract infections.

Chemical Phenomena↗