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Biomedical subjects

J T Doluisio

Publications and source records attributed to J T Doluisio.

At least 19 recordsLinked to original sources
PubMed1989

Positioning pharmacy for the 21st century.

There are always high expectations for a new year--and certainly we will have even higher expectations for a new century. To continue leadership in the 21st century, the American pharmaceutical industry must make a stronger commitment to new product research and development and the profession of pharmacy must commit to development of services needed for new, high-technology products and devices that will often be parenterally administered, bulky, nontraditional, patient-tailored, infrequently administered, and device-oriented. It is suggested that pharmacy must initiate efforts to include drug administration as a pharmaceutical service. Other actions are suggested to modify the curricula preparing pharmacists and to recruit a wider variety of students. A number of other professional initiatives are recommended and discussed to position pharmacy for enhanced clinical services. The issue of subperformance by pharmacists is discussed by pointing out that there is a significant difference in what often is, what should be, and what could be pharmacy service.

Forecasting↗
PubMed1986

Pharmacokinetics of orally administered pentoxifylline in humans.

The pharmacokinetics of pentoxifylline was studied in healthy male volunteers following single oral doses of 100, 200 and 400 mg of the drug in solution. Concentrations of the drug and three of its metabolites were determined in plasma. The major urinary metabolite was also determined for 24 hours after dosing. Pentoxifylline was rapidly and extensively absorbed at all doses. Peak plasma concentrations of pentoxifylline occurred between 0.29 and 0.41 hours after dosing. Its metabolites, a secondary alcohol and two homologous carboxylic acids showed tmax values from 0.72 to 1.15 hours. Cmax and AUC values increased in a dose-dependent manner for pentoxifylline and its metabolites over the three dose levels though strict dose proportionality could only be demonstrated for the principal carboxylic acid metabolite. The apparent plasma half-life of pentoxifylline varied between 0.39 and 0.84 hours for the various doses while the apparent half-lives of the metabolites were in the range of 0.96 to 1.61 hours. The major circulating metabolites, the secondary alcohol and carboxypropyl derivative, were at consistently higher plasma concentrations than the parent drug. Two major pathways account for the circulating metabolites of pentoxifylline though oxidation of the parent drug to a carboxylic acid accounts for the formation of the principal urinary elimination product. Because of the pharmacological activities of pentoxifylline, studies are proposed of the pharmacokinetic-pharmacodynamic correlations of pentoxifylline and its metabolites. The present pharmacokinetic results further support the use of a controlled-release dosage form of pentoxifylline for therapy.

Administration, Oral↗
PubMed1982

Disposition and absolute bioavailability of furosemide in healthy males.

Furosemide (40 mg) was administered to 18 healthy adult males as an intravenous dose, an oral solution, and in tablet form. The pharmacokinetics of intravenous furosemide were studied, determining a total body clearance rate of 117.6 +/- 41.3 ml/min and a harmonic mean half-life of 78 min. The mean absolute bioavailability determined by ratio of areas under the plasma-time curves was 64 and 71% for the solution and tablet, respectively. The mean absolute bioavailability determined by the ratio of urinary cumulative excretion data was 61 and 66% for the solution and tablet, respectively. The absolute bioavailability of furosemide determined with plasma and urine data were not significantly different. Thus, urine data alone may be used to establish bioavailability of furosemide. Inspection of plasma-time curves revealed secondary maxima in several subjects, suggesting enterohepatic cycling.

Administration, Oral↗
PubMed1980

Correlation of in vivo bioavailability of erythromycin stearate tablets with in vitro tests.

Correlations between the bioavailability parameters for erythromycin stearate tablets from five manufacturers and in vitro tests of these tablets were examined using forward (stepwise), multiple linear regression analysis. Bioavailability parameters were determined in clinical studies employing a balanced, incomplete block design. In vitro tests used disintegration, dissolution, and dissolution/dialysis as the independent variables in regression equations. Significant correlations were found between linear combinations of these parameters and the time of peak and the peak serum levels. The inclusion of an in vitro disintegration test to describe peak serum levels of erythromycin is noteworthy since it has been suggested that disintegration tests are of less value than dissolution techniques employed in the present investigation may be useful for selection of appropriate physicochemical tests for continued monitoring of the bioavailability of erythromycin stearate tablets.

Biological Availability↗
PubMed1979

Single-dose fasting bioequivalence assessment of erythromycin stearate tablets in man.

The bioequivalence of film-coated erythromycin stearate tablets produced by five different manufacturers was evaluated in a balanced incomplete block design involving the five formulations given to 30 fasted subjects over a 3-week study period. Serum levels of erythromycin activity were determined microbiologically. Statistical analysis of variance was performed on the observed bioavailability parameters: maximum serum concentration (Cmax), time to maximum serum concentration (Tmax), and area under the serum concentration-time curve (AUC). There was no statistical difference between formulations for the Tmax parameter. Formulation differences were found, however, based on the analysis of variance of the Cmax and AUC parameters. Two products, although not significantly different from one another, showed significantly greater Cmax and AUC values than the other three products.

Adult↗
PubMed1979

Plasma and tissue levels of furosemide in dogs and monkeys following single and multiple oral doses.

35S-Furosemide was administered to beagle dogs and rhesus monkeys as an oral solution on a single and a 20 repeated 5 mg/kg/day dosing regimen. In both species, furosemide is rapidly but incompletely absorbed with peak plasma levels being achieved within one hour after dosing. The plasma level versus time profiles do not appear to be significantly altered as a result of the repetitive dosing regimen employed, although the profiles themselves are quite different for the two species studied. Following single oral doses, the observed peak plasma levels achieved in dogs are approximately eight-fold higher than in monkeys. In dogs, oral administration of furosemide results in a biexponential disposition curve while in monkeys the profile appears monoexponential. The major disposition phase in dogs has a half-life or approximately 30 minutes and is followed by a slow elimination phase with a half-life of approximately 7 hours. Only a small percentage of the absorbed dose is affected by the slow disposition phase and consequently accumulation of furosemide on the once-daily dosing regimen is slight. In the monkey studies, the rapid disposition phase was not observed and the slow disposition phase had a half-life of approximately 11 hours. On the repetitive dosing regimen, the monkey appeared to accumulate furosemide to a slightly greater extnet than the dog and showed a lesser degree of fluctuation within a dosing interval. In both species, liver and kidney radioactivity levels were not detectable three days after a single dose although low levels of furosemide and/or metabolites were observed for six days following the last dose of the multiple dosing regimen. At the dosage level and regimen employed, no unusual or "typical" lesions associated with furosemide were found in the dog and monkey tissues examined histopathologically.

Administration, Oral↗
PubMed1978

Bioavailability of acetazolamide tablets.

Plasma acetazolamide levels were measured by an enzymatic assay following single 250-mg oral tablet doses to 20 healthy volunteers; five different lots of acetazolamide tablets from a single manufacturer were used in a balanced incomplete block design. From the measured plasma levels, estimates of the bioavailability parameters (area under the plasma concentration versus time curve, time to peak plasma concentration, and peak plasm concentration) were obtained by least-squares digital computer fitting. No significant differences among the tablets were observed (alpha = 0.05) for the analysis of variance of the area under the curve or time to peak parameters. Two tablets, however, provided statistically higher peak plasma concentrations than the other three. Thus, lot-to-lot bioinequivalence of acetazolamide tablets was observed. Some in vitro tests employed showed general trends for correlation with the in vivo data. However, considerable refinement of these technique appears necessary for in vitro prediction of the observed lot-to-lot bioinequivalence.

Acetazolamide↗
PubMed1978

Pentobarbital absorption from capsules and suppositories in humans.

Serum pentobarbital levels following administration of the sodium salt as a 100-mg capsule orally and as two 120-mg suppository formulations (A and B) rectally were measured. From these data and previously determined kinetic constants after intravenous administration, the absorption rates and bioavailability of pentobarbital from each dosage form were determined. All three dosage forms were 100% absorbed. Peak serum pentobarbital levels occurred at 1, 4, and 10 hr for the capsule, Suppository A, and Suppository B, respectively. In vitro studies agreed with the serum data in that Suppository A released drug in an in vitro aqueous pH 1.4 system at a much greater rate that Suppository B. The capsule and Suppository A both appeared to be absorbed by simple first-order processes; however, Suppository B had a complex absorption pattern, which was modeled using sequential zero-order and first-order absorption.

Administration, Oral↗
PubMed1977

Pharmacokinetics of orally administered hydroflumethiazide in man.

Hydroflumethiazide plasma and urine levels were measured fluorometrically following the oral administration of 100-mg doses (2 X 50 mg tablets) to each of 12 healthy, adult male subjects. The plasma level data as a function of time were fit to a one-compartment open model using a nonlinear regression digital computer program. The means of the individual apparent absorption and disposition rate apparent absorption and disposition rate constants were 0.770+/-0.46 hr(-1) (t1/2=0.9 hr) and 0.358+/-0.17 hr(-1) (t1/2=1.94 hr), respectively, with a 0.49+/-0.26 hr lag time in absorption. The same parameter estimates obtained by fitting the mean plasma concentration-time curve were 0.461+/-0.15 hr(-1), 0.357+/-0.13 hr(-1), and 0.39+/-0.09 hr for the apparent absorption and disposition rate constants and the lag time, respectively. The closeness of the parameter estimates and the lack of intravenous data preclude unequivocal assignment of the rate constants to the absorption or disposition processes. Nevertheless, the disposition of hydroflumethiazide is clearly a rapid process. The means of the individual peak plasma levels and times to peak were 0.301+/-0.94 microgram/ml and 2.12+/-0.59 hours, respectively. The mean area under the plasma level-time curve was 1.95+/-0.78 microgram-hr/ml and 46.7+/-20.0% of the administered dose was recovered in the 24-hour urine. The mean renal clearance of hydroflumethiazide was 453.4+/-256.6 ml/min.

Administration, Oral↗
PubMed1976

Absorption, distribution, metabolism, and excretion of furosemide in dogs and monkeys I: analytical methodology, metabolism, and urinary excretion.

35S-Furosemide was administered to beagle dogs and rhesus monkeys in an oral solution on a single and a 20 repeated 5-mg/kg/day dosing regimen. Following the single dose, 25.0% (dogs) and 24.0% (monkeys) of the dose were excreted in the urine in 24 hr. TLC analysis demonstrated that both species had similar excretory patterns; i.e., over 80% of the amount excreted in the urine was present as unchanged durosemide and the remainder was composed of a known metabolite, saluamine, and an as yet unidentified metabolite(s). The repetitive dosing regimen did not appear to alter significantly either the total amount recovered in the 24-hr urine or the excretion pattern. Studies in dogs showed that only 50-60% of furosemide was absorbed from oral solution. A significant biliary secretion elimination pathway for furosemide also was observed.

Animals↗
PubMed1976

Inhibition of sporulation by cerulenin and its reversion by exogenous fatty acids in Saccharomyces cerevisiae.

Sporulation of Saccharomyces cerevisiae G2-2 was inhibited by the antibiotic cerulenin which is known to be a specific inhibitor of fatty acid and sterol synthesis. This inhibition was reversed by various fatty acids, especially by oleic acid (C(18:1)) and pentadecanoic acid (C(15:0)). Ergosterol showed only slight reversibility of this inhibition. When cerulenin was added to the sporulation medium later than 12 h after the start of incubation, the marked inhibition disappeared. When the fatty acid fraction extracted from the sporulated yeasts was added to the cells pretreated with cerulenin for more than 6 h, sporulation became evident 6 h after the fatty acid fraction addition. Therefore, sufficient synthesis of fatty acids required for sporulation was assumed to occur during the first 6 h in phase I of yeast sporulation.

Antifungal Agents↗
PubMed1976

R-factor-mediated resistance to sulfonamides by a plasmid-borne, drug-resistant dihydropteroate synthase.

Evidence was found for the existence of an episome-specified variant of the enzyme dihydropteroate synthase involved in folic acid formation. Since the plasmid-borne enzyme showed a decreased susceptibility for sulfonamide inhibition and was transferable together with resistance to this drug, it is proposed that diploidy for the target enzyme in some cases could be the mechanism of R-factor-mediated resistance to sulfonamides. Two types of evidence were obtained. One was the rescue from temperature sensitivity of bacterial mutants with a lesion in the chromosomal dihydropteroate synthase by the R factor R1dr19 mediating sulfonamide resistance. The other evidence was found by the determination of dihydropteroate forming activity in extracts from R(-) and R(+) bacteria. Cells harboring R1dr19 were found to contain an enzyme activity which was far less susceptible to sulfonamide inhibition than the corresponding activity from R(-) cells.

Dihydropteroate Synthase↗
PubMed1975

Drug absorption VII: influence of mesenteric blood flow on intestinal drug absorption in dogs.

Intestinal absorption of sulfaethidole and haloperidol was determined using an in situ canine intestinal preparation. Intestinal absorption of sulfaethidole was determined at three or four mesenteric blood flow rates in each dog, ranging from unaltered flow (100%) to no flow (0%). A relatively small change in absorption rate occurred when the splanchnic blood flow rate was decreased about 35%. Further reductions in mesenteric blood flow resulted in progressive impairment of sulfaethidole absorption. The simultaneous measurement of sulfaethidole intestinal disappearance and appearance in blood indicates that sulfaethidole disappearance is equivalent to absorption. Haloperidol absorption also decreased with decreased intestinal perfusion but differed from sulfaethidole in that membrane storage of haloperidol appeared to take place during its absorption.

Animals↗