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45 results on '"Harrison, Lester I."'

3. Cutaneous Pharmacodynamics of a Toll-Like Receptor 7 Agonist, 852A, in Humans

Author

Astry, Calvin, Birmachu, Woubalem, Harrison, Lester I., and Meng, Tze-Chiang

Subjects
Agonists (Biochemistry) -- Physiological aspects -- Properties -- Research, Gene expression -- Research -- Physiological aspects, Pharmacokinetics -- Research -- Physiological aspects, Health, Physiological aspects, Research, Properties
Abstract

Byline: Calvin Astry, PhD (Department of Medical and Scientific Affairs, 3M Pharmaceuticals); Woubalem Birmachu, PhD (Department of Pharmacology, 3M Pharmaceuticals); Lester I. Harrison, PhD (Department of Pharmacokinetics/Drug Metabolism 3M Pharmaceuticals, [...]

Published
2008
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10. Abstract 1475: Local immune activation resulting in tumor growth inhibition with MEDI9197 - an intratumorally administered TLR7/8 agonist

Author

Mullins, Stefanie, primary, Grigsby, Iwen, additional, Harrison, Lester I., additional, Ren, Song, additional, Soukharev, Serguei, additional, Young, Lesley, additional, Elvecrog, James M., additional, Wilkinson, Robert W., additional, Tomai, Mark A., additional, Herbst, Ronald, additional, Vasilakos, John P., additional, and Leishman, Andrew J., additional

Published
2016
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29. Kinetics of Absorption of a New Once-a-Day Formulation of Theophylline in the Presence and Absence of Food

Author

Harrison, Lester I., primary, Mitra, Amit K., additional, Kehe, Colin R., additional, Klinger, Nancy M., additional, Wick, Karen A., additional, Mccarville, Sally E., additional, Cooper, Kathy M., additional, Chang, Shaw F., additional, Roddy, Patrick J., additional, Berge, Steve M., additional, Kisicki, James C., additional, and Dockhorn, Robert, additional

Published
1993
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33. Plasma and urine levels of flumequine and 7-hydroxyflumequine following single and multiple oral dosing.

Author

Schuppan, Dietrich, Harrison, Lester I., Rohlflng, Stephen R., Miller, Howard L., Funk, Mary L., Hansen, Chad S, Ober, Robert E, Schuppan, D, Harrison, L I, Rohlfing, S R, Miller, H L, Funk, M L, Hansen, C S, and Ober, R E

Subjects
BIOTRANSFORMATION (Metabolism), HETEROCYCLIC compounds, ORAL drug administration, QUINOLONE antibacterial agents
Abstract

Plasma and urine concentrations of flumequine and its microbiologically active metabolite, 7-hydroxyflumequine, were determined in healthy subjects following single oral doses of 400, 800, and 1200 mg of flumequine, and following multiple oral doses of 800 mg given four-times daily. After administration of the single oral doses, antimicrobial levels in plasma and urine were rapidly attained, were proportional to the dose given, and were maintained for 12 to 24 h. The multiple dosage regimen yielded antimicrobial levels in both plasma and urine that were several-fold higher than the levels required to inhibit the growth of susceptible bacteria. Following both the single and multiple dose regimens, the plasma elimination half-life of flumequine was about 7h. The excretion of 7-hydroxyflumequine in the urine contributed significantly to the antimicrobial activity. [ABSTRACT FROM AUTHOR]

Published
1985

38. Absorption, Biotransformation, and Pharmacokinetics of Salicylsalicylic Acid in Humans.

Author

HARRISON, LESTER I., FUNK, MARY L., RÉ, OZVALDO N., and OBER, ROBERT E.

Abstract

The absorption, biotransformation, and pharmacokinetics of the antiinflammatory drug salicylsalicylic acid (SSA) were studied. Healthy adult males received 1000 mg SSA and 1300 mg aspirin according to a crossover design either as a single oral dose (12 subjects) or three times a day for five days (4 subjects). A newly developed, high-pressure liquid chromatographic assay permitted selective, direct measurement of SSA in the presence of high concentrations of salicylic acid, one of its metabolites. Following a single dose, SSA was promptly absorbed (mean time to peak level 1.5 hour) and was eliminated from plasma with a mean half-life of 1.1 hour. Less than 1 per cent was excreted in the urine as unchanged SSA. SSA did not accumulate in the plasma during multiple dosing. Plasma levels of salicylic acid following single and multiple doses of SSA indicate that SSA is extensively hydrolyzed to salicylic acid in the body. The slightly lower levels of salicylic acid after SSA than after aspirin may reflect direct biotransformation of some of the SSA to an SSA conjugate, without hydrolysis to salicylic acid. [ABSTRACT FROM AUTHOR]

Published
1981
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39. Local versus Total Systemic Bioavailability of Beclomethasone Dipropionate CFC and HFA Metered Dose Inhaler Formulations

Author

Harrison, Lester I.

Abstract

For inhaled formulations, the balance between desired local effects and undesired systemic activity can be expressed by L/T, where L represents bioavailability of drug from the lungs and T represents total systemic bioavailability. L/T is most useful when comparing formulations of the same inhaled substance. A high L/T is desirable as this implies efficient drug delivery to the target site, and minimization of unwanted activity from non-targeted drug delivery. The objective of this publication is to compare L/T for CFC and HFA inhaler formulations of beclomethasone dipropionate (BDP). Predictions of the L/T comparison were tested with clinical trials. From five deposition and pharmacokinetic studies, L/T ratios for CFC-BDP and HFA-BDP were calculated as 0.21 and 0.92, respectively. These ratios predicted two differences for the therapeutic use of these products: (1) a smaller dose of HFA-BDP than CFC-BDP may be required for efficacy; and (2) a smaller number of adverse events may be observed for the HFA-BDP product, when delivered at the equivalent dose, compared to the CFC comparitor. A dose-response study confirmed that less than half the dose of HFA-BDP is needed to give the same efficacy as CFC-BDP. Two safety studies that measured adrenal suppression demonstrated less suppression with HFA-BDP than with a comparable efficacious dose of CFC-BDP. It is concluded that L/T is a useful parameter that incorporates the systemic contributions of lung deposition and pharmacokinetics. It is recommended that this parameter be considered whenever deposition and pharmacokinetic data for two formulations of the same inhaled substance are compared.

Published
2002
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40. Physiologically Based Pharmacokinetic Model for Digoxin Disposition in Dogs and Its Preliminary Application to Humans

Author

Harrison, Lester I. and Gibaldi, Milo

Abstract

A physiologically based pharmacokinetic model for digoxin disposition developed in the rat was modified to account for the interspecies differences in tissue-to-plasma digoxin concentration ratios and applied to the dog. The model provided a quantitative assessment of the time course of digoxin concentrations in dog plasma, various tissues, and urine. It also predicted the effect of renal failure on digoxin pharmacokinetics in the dog. An attempt to scale the dog model to humans by simply considering differences in organ volumes, organ flow rates, and digoxin clearances was partially successful. Good predictions of plasma digoxin concentration and urinary digoxin excretion after a single dose and of steady-state plasma, heart, and skeletal muscle digoxin concentrations were obtained. However, the model predicted considerably higher kidney digoxin concentrations than are actually found. Although the model adequately characterized the time course of digoxin concentrations in patients with moderate renal impairment, it provided a relatively poor fit to that observed in anuric patients.

Published
1977
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41. Physiologically Based Pharmacokinetic Model for Digoxin Distribution and Elimination in the Rat

Author

Harrison, Lester I. and Gibaldi, Milo

Abstract

A plasma flow rate-limited pharmacokinetic model was developed to describe the distribution of digoxin to the heart, liver, kidneys, skeletal muscle, and GI tract in the rat. The model also provides for renal, hepatic (metabolic and biliary), and GI clearance as well as for biliary and Gl secretion and GI reabsorption of digoxin. Predicted concentrations of digoxin in the heart, liver, skeletal muscle, and plasma were consistent with experimental observations in conscious rats after an intravenous dose. The model was extended to describe digoxin concentrations in the plasma of bile duct-ligated rats and ureter-ligated rats, simply by modifying appropriate clearance parameters. Excellent agreement was obtained between predicted and observed urinary excretion rates of digoxin for 12hr after an intravenous dose to normal and bile duct-ligated rats.

Published
1977
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45. Comparative Absorption of Atropine from a MeteredDose Inhaler and an Intramuscular Injection

Author

Kehe, Colin R., Lasseter, Kenneth C., Miller, Nicholas C., Wick, Karen A., Shamblen, E. Cooper, Ekholm, Bruce P., Sandahl, Jane H., Chang, Shaw F., Goldlust, M. Barry, Kvam, Donald C., and Harrison, Lester I.

Abstract

The inhalation of atropine sulfate from a pressurized metered-dose inhaler was investigated in a nonrandomized four-period rising-dose study. Eight healthy, nonsmoking subjects received 1.7, 3.4, and 5.2 mg of atropine sulfate by inhalation and 1.67 mg of atropine free base (equivalent to 2 mg of atropine sulfate) by intramuscular (i.m.) injection. Serum atropine sulfate concentrations were measured over a 24-h period by gas chromatography/mass spectrometry. Mean serum concentrations increased nonproportionally as the inhaled dose increased. Mean peak concentrations were 4.9, 6.1, and 7.9 ng/ml for the inhaled doses and 8.4 ng/ml for the i.m. dose. Typical anticholinergic effects were seen after all doses.

Published
1992

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