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Biomedical subjects

S M Wallace

Publications and source records attributed to S M Wallace.

At least 37 records · Page 2Linked to original sources
PubMed1984

Establishing a clinical pharmacokinetic service for gentamicin in a community hospital.

To assess the feasibility and acceptability of a pharmacy-based clinical pharmacokinetic service for gentamicin, serum gentamicin levels were measured by radioimmunoassay in 44 patients hospitalized during a three-month period in an acute-care general hospital. Serum levels measured pre- and post-infusion were used to estimate pharmacokinetic parameters and optimum dosage regimens for individual patients. Based on serum level measurements of gentamicin, 30% of patients required no dosage adjustment, 23% an increase in dose and 47% a decrease in dose. Of the 30 changes recommended, 83% were implemented by physicians. Monitoring serum levels and adjusting dosage reduced the number of patients with sub-therapeutic and toxic serum levels. Adjusting dosage with the aid of serum levels appeared to be most useful for the elderly patient or the patient with impaired kidney function. Initial choice of dosage regimens for patients would be improved by appropriate use of the Hull and Sarubbi dosing nomogram (with certain modifications) or method of estimating pharmacokinetic parameters. The Hull and Sarubbi method was considered preferable to the dosing recommendation of 1.1 mg/kg at an interval of eight times the serum creatinine value. Excellent physician acceptance of a gentamicin serum level monitoring service was demonstrated in terms of the physician's usage of the service and implementation of the pharmacist's recommendations. A multidisciplinary approach involving medicine, pharmacy, nursing and laboratory staff was essential for successful operation of the pharmacokinetic service. However, the responsibility for the development and overall coordination of the pharmacokinetic service should remain with the pharmacist.

Gentamicins↗
PubMed1984

Evaluation of a computer-assisted medication refill reminder system for improving patient compliance.

Computer-generated refill reminder notices were mailed to patients receiving continual medication for cardiovascular diseases to measure improved compliance and to discover whether a computer-assisted program was economically viable. Guidelines were established to define compliance. A computer-assisted compliance intervention program did not significantly improve the rate at which patients had their prescriptions filled "on time" and the mean compliance rate for both experimental and control groups was greater than 79%. Also discussed were cost and compliance strategy implications and the receptiveness of patients to the reminder program.

Analysis of Variance↗
PubMed1984

Effect of age and sex on the plasma binding of acidic and basic drugs.

Protein binding of chlorpromazine, propranolol, meperidine, desipramine, salicylic acid and phenytoin was determined in plasma of 64 healthy volunteers (35 males and 29 females). An attempt was made to identify factors affecting the plasma protein binding of these drugs. Whereas plasma albumin levels decreased as a function of age in both sexes, alpha 1-acid glycoprotein levels increased with age, but the increase was more pronounced in males. The free plasma fraction of the acidic drugs (salicylic acid, phenytoin) and desipramine (a base) showed a significant (p less than 0.005) negative correlation with plasma albumin levels. The free fractions of the other three basic drugs (chlorpromazine, propranolol, meperidine) in plasma showed a significant (p less than 0.005) negative correlation with alpha 1-acid glycoprotein plasma levels. Plasma protein binding of salicylic acid, phenytoin and desipramine decreased as a function of age. Plasma protein binding of chlorpromazine, propranolol and meperidine was virtually unaffected by age or was slightly increased (chlorpromazine). Only in the case of salicylic acid could a statistically significant difference be demonstrated between males and females in the free fraction-age relationship. Stepwise multiple linear regression analysis, including age and blood chemistry values such as hematocrit, bilirubin, cholesterol, triglycerides, creatinine, BUN, albumin and alpha 1-acid glycoprotein as independent variables, identified age as the variable explaining most of the variability in plasma binding of salicylic acid, phenytoin and desipramine. For chlorpromazine, propranolol and meperidine alpha 1-acid glycoprotein was the most important determinant of plasma protein binding.

Adolescent↗
PubMed1983

Methaqualone-diphenhydramine interaction study in humans.

Twelve healthy subjects received three single oral doses (250 mg) of methaqualone alone or in combination with diphenhydramine (25 mg). Blood samples were collected for a 48-hr period after each dose and analyzed for methaqualone and its major metabolite, 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone. Peak blood concentrations ranging from 1.0 to 2.7 micrograms/ml occurred approximately 1-2 hr after the oral dose. The area under the blood level-time curve, peak plasma level, and elimination half-life for methaqualone were not significantly different (three-way ANOVA, p greater than 0.05) when methaqualone was administered alone, in combination with a diphenhydramine elixir or as a commercial product (capsule) containing both methaqualone and diphenhydramine. Statistically significant intersubject differences in the area under the curve were eliminated if the area was corrected for subject differences in elimination. Blood levels of the metabolite reached an average peak of 314 ng/ml (+/- 107) between 4 and 8 hr after the dose and remained elevated for the 48-hr sampling period. The areas under the blood level time curve of the metabolite were not significantly different for the three treatments. Diphenhydramine administered at the dosage level used in therapeutic combination products did not alter the blood levels of methaqualone or its metabolite. In addition, no significant differences in methaqualone availability from the two commercial formulations tested could be detected.

Adult↗
PubMed1979

Skin levels and vasoconstrictor assay of topically applied hydrocortisone.

Ointment containing 2.5% hydrocortisone was applied topically under occlusion to 84 subjects. Fifty-three percent of the population showed skin blanching in response to topical application of the steroid. To correlate vasoconstrictor response with drug level, hydrocortisone concentrations were determined fluorometrically in skin samples from 16 subjects in whom skin blanching was also assessed. The epidermal concentration of hydrocortisone was significantly greater in those subjects who exhibited blanching. Data suggest that a minimum epidermal reservoir of 200 micrograms of hydrocortisone per gram of lyophilized tissue is necessary to elicit a definite vasoconstrictor response.

Administration, Topical↗
PubMed1978

Effect of diphenhydramine on methaqualone metabolism: an in vitro study.

A GLC assay to quantitate the methaqualone metabolite 2-methyl-3-(2-hydroxymethylphenyl)-4(3H)-quinazolinone was developed. Standard curves were linear, and recovery of the metabolite from tissue homogenates averaged 89%. In vitro metabolism of methaqualone by the 10,000Xg supernatant fraction of rat liver homogenate was measured by monitoring metabolite formation with the GLC assay. Diphenhydramine inhibited the in vitro metabolism of methaqualone. The percentage inhibition increased with increasing diphenhydramine concentration. The significance of this inhibition in relation to use and abuse of methaqualone--diphenhydramine combinations is discussed.

Animals↗
PubMed1978

Pharmacokinetic analysis of percutaneous absorption: evidence of parallel penetration pathways for methotrexate.

Compartmental models were developed to describe the penetration of a drug from a topically applied vehicle through the skin. Data for in vitro penetration of methotrexate through hairless mouse skin from vehicles varying in pH from 3.5 to 6.5 were computer-fitted to estimate model parameters. Comparison of lag time and the exponential coefficient suggested that parallel penetration pathways exist. The fraction of drug penetrating through the shunt pathway increased as vehicle pH and ionization increased. Penetration curves were quantitatively partitioned into bulk tissue and shunt contributions. At pH 6.5, flux through the shunt pathway predominated.

Animals↗
PubMed1977

Topically applied antifungal agents. Percutaneous penetration and prophylactic activity against trichophyton mentagrophytes infection.

Penetration and prophylactic activity against Trichophyton mentagrophytes infection of topically applied antifungal agents were studied in human volunteers. The concentration and persistence of drug in the stratum corneum was determined after different treatment schedules and from different vehicles. Measurable levels of griseofulvin, clotrimazole, miconazole nitrate, and thiabendazole remained in the skin four days after discontinuation of topical applications. Griseofulvin, miconazole, and clotrimazole exhibited prophylactic activity against infection by T mentagrophytes spores in a standardized test. Griseofulvin was a significantly better prophylactic agent than either miconazole or clotrimazole.

Administration, Topical↗
PubMed1977

GLC analysis of acetazolamide in blood, plasma, and saliva following oral administration to normal subjects.

An electron-capture GLC assay for acetazolamide in biological fluids was developed. Extraction efficiency was 69-104%. The minimum detectable amount of acetazolamide was 10 ng/sample. Concentrations of acetazolamide were determined by GLC in blood, plasma, plasma water, and saliva after oral administration of a single 250-mg dose to five volunteers. Erythrocyte levels were calculated from whole blood and plasma data. Concentration of free drug in the plasma was measured in samples of plasma water obtained by microultrafiltration. Peak plasma levels of 10-18 microng/ml were reached 1-3 hr after the dose. At least 1 hr later, erythrocyte levels reached peak concentrations of 13-29 microng/ml. Over 31 hr, plasma levels declined more rapidly than erythrocyte levels. Saliva concentrations averaged 1% of those in plasma and decreased at a rate equal to that of plasma. Saliva levels were proportional to, but not equal to, water concentration. Saliva to plasma ratios were consistent for any given individual and, therefore, offer a means of monitoring drug dosage without resorting to frequent blood sampling.

Acetazolamide↗