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The pharmacokenetics of sodium cromoglycate

The pharmacokenetics of sodium cromoglycate
The pharmacokenetics of sodium cromoglycate

Sodium cromoglycate (SCG) is a small water soluble molecule which is well absorbed from the respiratory tract with over 70% bioavailability. In contrast less than 1% is absorbed from the mouth and gastro-intestinal tract. After inhalation the majority of SCG that reaches the plasma comes from the respiratory tract. Following inhalation of SCG from a Spinhaler the plasma pharmacokinetics fit a one-compartment model with absorption rate limited characteristics. Inspiratory flow rate (IFR) is the most important factor in determining the dose reaching the lungs, but breath-hold had no effect. Asthmatic and normal subjects showed no differences in the plasma pharmacokinetics of SCG. Inhaled adenosine monophosphate (AMP) causes broncho-constriction in asthmatic subjects which is strongly antagonised by SCG. The degree of protection was correlated to the IFR at which the SCG was inhaled and to the plasma concentration represented either as a peak level or the area under the plasma concentration/time curve. Nedocromil sodium, a compound related to SCG, was found to be 4-8 times more potent than SCG in antagonising the bronchoconstrictor effects of AMP. The presence of bronchoconstriction causes more central deposition of nebulised SCG, but has no effect on the plasma pharmacokinetics. However the deposition patterns were significantly more central in normal than asthmatic subjects for the same degree of constriction; suggesting a difference in airway response. Lung epithelial permeability is known to affect the absorption of low molecular weight substances. Both inhaled histamine and deep inspiration increase the clearance of SCG from the lung for a short period of time. Whether a more prolonged alteration of permeability would affect the duration of action of SCG is unknown.

University of Southampton
Richards, Robert
Richards, Robert

Richards, Robert (1989) The pharmacokenetics of sodium cromoglycate. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Sodium cromoglycate (SCG) is a small water soluble molecule which is well absorbed from the respiratory tract with over 70% bioavailability. In contrast less than 1% is absorbed from the mouth and gastro-intestinal tract. After inhalation the majority of SCG that reaches the plasma comes from the respiratory tract. Following inhalation of SCG from a Spinhaler the plasma pharmacokinetics fit a one-compartment model with absorption rate limited characteristics. Inspiratory flow rate (IFR) is the most important factor in determining the dose reaching the lungs, but breath-hold had no effect. Asthmatic and normal subjects showed no differences in the plasma pharmacokinetics of SCG. Inhaled adenosine monophosphate (AMP) causes broncho-constriction in asthmatic subjects which is strongly antagonised by SCG. The degree of protection was correlated to the IFR at which the SCG was inhaled and to the plasma concentration represented either as a peak level or the area under the plasma concentration/time curve. Nedocromil sodium, a compound related to SCG, was found to be 4-8 times more potent than SCG in antagonising the bronchoconstrictor effects of AMP. The presence of bronchoconstriction causes more central deposition of nebulised SCG, but has no effect on the plasma pharmacokinetics. However the deposition patterns were significantly more central in normal than asthmatic subjects for the same degree of constriction; suggesting a difference in airway response. Lung epithelial permeability is known to affect the absorption of low molecular weight substances. Both inhaled histamine and deep inspiration increase the clearance of SCG from the lung for a short period of time. Whether a more prolonged alteration of permeability would affect the duration of action of SCG is unknown.

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Published date: 1989

Identifiers

Local EPrints ID: 462061
URI: http://eprints.soton.ac.uk/id/eprint/462061
PURE UUID: 32ae843c-35cc-442b-bdeb-1438da5d4189

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Date deposited: 04 Jul 2022 19:00
Last modified: 04 Jul 2022 19:00

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Contributors

Author: Robert Richards

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