Measurement of human lung absorption of metaproterenol given via an aerosol using a stable isotope approach

MacGregor, T R

Title: Measurement of human lung absorption of metaproterenol given via an aerosol using a stable isotope approach

Full Record
Other Related Research

Abstract

The extent and rate of lung absorption of metaproterenol given via a metered dose aerosol was studied in normal, asthmatic, and chronic bronchitic volunteers. Aerosols of metaproterenol-d/sub 0/ and metaproterenol-/sup 13/C/sub 3/, 650 mcg doses each, were utilized followed in 3 hours by a 980 mcg intravenous infusion of metaproterenol-d/sub 7/. Pharmacokinetics of all three stable isotope formulations were studied in a 24 hour period in conjunction with pharmacologic effect measurements. A gas chromatographic/mass spectrometric assay for metaproterenol capable of reliably measuring plasma concentrations as low as 50 pg/mL was developed. Extent of lung absorption of metaproterenol following aerosol administration averaged 3% in normal and asthmatic volunteers (N = 6 each) and 1.8% in chronic bronchitic volunteers (N = 5). The extent absorbed on the second dose was comparable to the extent from the first dose. The rates of lung absorption, calculated by the Loo-Riegelman method, were bi-phasic in all volunteers with an initial, rapid first order phase followed by a slower, zero order phase. A working hypothesis, based on the solid suspension properties of the aerosol, was presented.

Authors:: MacGregor, T R

Publication Date:: Tue Jan 01 00:00:00 EST 1985

Research Org.:: Connecticut Univ., Storrs (USA)

OSTI Identifier:: 6937469

Resource Type:: Thesis/Dissertation

Resource Relation:: Other Information: Thesis (Ph. D.)

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; SYMPATHOMIMETICS; UPTAKE; AEROSOLS; ASTHMA; BLOOD PLASMA; BRONCHITIS; CARBON 13; CHEMOTHERAPY; GAS CHROMATOGRAPHY; IN VIVO; LABELLED COMPOUNDS; LUNGS; MASS SPECTROSCOPY; TRACER TECHNIQUES; AUTONOMIC NERVOUS SYSTEM AGENTS; BIOLOGICAL MATERIALS; BLOOD; BODY; BODY FLUIDS; CARBON ISOTOPES; CHROMATOGRAPHY; COLLOIDS; DISEASES; DISPERSIONS; DRUGS; EVEN-ODD NUCLEI; ISOTOPE APPLICATIONS; ISOTOPES; LIGHT NUCLEI; MATERIALS; NUCLEI; ORGANS; RESPIRATORY SYSTEM; RESPIRATORY SYSTEM DISEASES; SEPARATION PROCESSES; SOLS; SPECTROSCOPY; STABLE ISOTOPES; THERAPY; 551000* - Physiological Systems

Citation Formats


                    MacGregor, T R. Measurement of human lung absorption of metaproterenol given via an aerosol using a stable isotope approach.  United States: N. p., 1985. 
        Web.

Copy to clipboard


                    MacGregor, T R. Measurement of human lung absorption of metaproterenol given via an aerosol using a stable isotope approach.  United States.

Copy to clipboard


                    MacGregor, T R. 1985.  
        "Measurement of human lung absorption of metaproterenol given via an aerosol using a stable isotope approach".  United States.

Copy to clipboard


                    
@article{osti_6937469,

  title        = {Measurement of human lung absorption of metaproterenol given via an aerosol using a stable isotope approach},

  author       = {MacGregor, T R},

  abstractNote = {The extent and rate of lung absorption of metaproterenol given via a metered dose aerosol was studied in normal, asthmatic, and chronic bronchitic volunteers. Aerosols of metaproterenol-d/sub 0/ and metaproterenol-/sup 13/C/sub 3/, 650 mcg doses each, were utilized followed in 3 hours by a 980 mcg intravenous infusion of metaproterenol-d/sub 7/. Pharmacokinetics of all three stable isotope formulations were studied in a 24 hour period in conjunction with pharmacologic effect measurements. A gas chromatographic/mass spectrometric assay for metaproterenol capable of reliably measuring plasma concentrations as low as 50 pg/mL was developed. Extent of lung absorption of metaproterenol following aerosol administration averaged 3% in normal and asthmatic volunteers (N = 6 each) and 1.8% in chronic bronchitic volunteers (N = 5). The extent absorbed on the second dose was comparable to the extent from the first dose. The rates of lung absorption, calculated by the Loo-Riegelman method, were bi-phasic in all volunteers with an initial, rapid first order phase followed by a slower, zero order phase. A working hypothesis, based on the solid suspension properties of the aerosol, was presented.},

  doi          = {},

  url          = {https://www.osti.gov/biblio/6937469},
  journal      = {},
number       = ,

  volume       = ,

  place        = {United States},

  year         = {Tue Jan 01 00:00:00 EST 1985},

  month        = {Tue Jan 01 00:00:00 EST 1985}

}

Copy to clipboard

Thesis/Dissertation:

Other availability

Please see Document Availability for additional information on obtaining the full-text document. Library patrons may search WorldCat to identify libraries that hold this thesis or dissertation.

Save / Share:

Export Metadata

Save to My Library

Similar records in OSTI.GOV collections:

Effect of metaproterenol sulfate on mild asthmatics' response to sulfur dioxide exposure and exercise

Journal Article Linn, W; Avol, E; Shamoo, D; ... - Arch. Environ. Health; (United States)

Twenty asthmatic volunteers, most with mild disease, underwent dose-response studies with sulfur dioxide (SO2) under three pretreatment conditions: (1) drug (metaproterenol sulfate in aerosolized saline solution), (2) placebo (aerosolized saline only), and (3) no pretreatment. Sulfur dioxide exposure concentrations were 0.0, 0.3, and 0.6 ppm. Experimental conditions were presented in random order at 1-wk intervals. Exposures lasted 10 min with heavy continuous exercise. Lung function was measured at baseline, after pretreatment (immediately pre-exposure), immediately post-exposure, and during a 2-hr follow-up. Subjects could elect to take bronchodilators during follow-up. Symptoms were monitored before, during, and for 1 wk after exposure. Withmore »« less
https://doi.org/10.1080/00039896.1988.9935858
Distribution and chloramphenicol in the bovine genital tract and pharmacokinetic studies of florfenicol in cattle

Thesis/Dissertation Bretzlaff, K

The objectives were to investigate selected aspects of the distribution of chloramphenicol (CAP) in the bovine genital tract and to conduct preliminary pharmacologic studies with florfenicol (FLO), a fluorinated analogue of thiamphenicol, in cattle. After 8 hours' continuous intravenous (IV) infusion of CAP to 7 postpartum cows, steady state plasma-to-genital tissue ratios of CAP were approximately 3. After intrauterine infusion of 20 mg CAP/kg to 3 postpartum cows, approximately 40% of the dose was absorbed into the bloodstream. Tissue concentrations were high at 8 hour postdosing in tissues lining the uterine lumen but were below desired therapeutic concentrations in themore »« less
Responses to sulfur dioxide and exercise by medication-depend asthmatics: Effect of varying medication levels

Journal Article Linn, W; Shamoo, D; Peng, R; ...

Twenty-one volunteers with moderate to severe asthma were exposed to sulfur dioxide (SO{sub 2}) at concentrations of O (control), 0.3, and 0.6 ppm in each of three medication states: (1) low (much of their usual asthma medication withheld), (2) normal (each subject on his own usual medication schedule), and (3) high (usual medication supplemented by inhaled metaproterenol before exposure). Theophylline, the medication usually taken by subjects, was often supplemented by beta-adrenergics. Exposures were for 10 min and were accompanied by continuous heavy exercise (ventilation {approximately} 50 1/min). Lung function and symptoms were measured before and after exposure. With normal medication,more »« less
Quantitative aspects of 1-norepinephrine induced pathologic changes: a study in normal dogs

Conference Szakacs, J; Mehlman, B

The effects of constant rate intravenous infusions of norepinephrine were studied in 28 normal dogs, sedated with morphine. The range of dose rates in this experiment was from 0.5 to 15 mcg/min/kg. Blood levels of epinephrine and norepinephrine were determined in 12 animals up to 10 hours during constant rate infusions. The heart rate and blood pressure were recorded in frequent intervals. The reflex bradycardia was reversed in the animals by prolonged infusions of one or more mcg/min/kg of norepinephrine. Tachycardia and arrhythmia were regularly present in the animals that developed myocardial lesions. Death occurred due to cardiac arrest, massivemore »« less
Sulfuric acid aerosol followed by ozone exposure in healthy and asthmatic subjects

Journal Article Frampton, M; Morrow, P; Cox, C - Environmental Research

These studies evaluated symptom and pulmonary function responses of humans sequentially exposed to sulfuric acid aerosol and ozone. Thirty healthy subjects and 30 allergic asthmatic subjects underwent 3-hr exposures in an environmental chamber to 100{mu}g/m{sup 3} sulfuric acid and sodium chloride (control) aerosols (in random order), followed 24 hr later by 3-hr exposures to ozone (0.08, 0.12, or 0.18 ppm). Each subject was studied four times, receiving each aerosol preexposure followed by two of the three ozone concentrations. For the healthy group, no convincing symptomatic or physiologic effects of exposure to either the aerosol or ozone on lung function weremore »« less
https://doi.org/10.1006/enrs.1995.1020

Similar Records