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Title: The radiolabelling of salbutamol with technetium-99m and its applications to the study of salbutamol deposition in the human respiratory tract
Author: Biddiscombe, Martyn Francis
ISNI:       0000 0001 3463 7462
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1994
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Radionuclide imaging has the potential to provide a non-invasive and accurate means of obtaining information about the location and movement of an in-vivo distribution of labelled drug. Its application to inhaled drugs used for the treatment of diseases of the airways has been limited due to the difficulty in attaching suitable radionuclides. Most information has been obtained by using less accurate indirect methods, which require an inert substitute to be labelled instead, or by measuring concentrations of drug and metabolite in mouth washings, blood and urine. In 1988 a method was described that permits the direct radiolabelling of beta2-agonists in pressurised metered-dose inhalers (MDI) with the gamma-emitting radionuclide technetium-99m (Kohler et al, 1988). However, this method has some criticisms and is not applicable to dry powder inhalers (DPIs). A new method, based on that of Kohler, has been developed and reported in this thesis, which enables the betaj-agonist salbutamol to be directly radiolabelled with technetium- 99m in both MDIs and DPIs. The technique was validated using an Andersen cascade impactor and used to study ten normal volunteers and nineteen patients with asthma. On separate days, subjects inhaled 200 [mu]g of salbutamol from a DPI, an MDI and an MDI via a spacer. The drug was administered under conditions as close as possible to those in which subjects would normally use their inhalers. Inspiratory flow profiles were measured while subjects inhaled from the MDI and DPI. The proportions of dose depositing in the lungs, throat and stomach were quantified using a dual headed gamma camera. Bronchodilator response was determined by measuring lung function parameters before and after administration. Higher lung drug deposition values were measured than had been reported using indirect labelling techniques. The mean (sd) lung deposition for the normals and asthmatics respectively were 12.4 (3.5)% and 11.4 (5.0)% for the DPI, 21.6 (8.9)% and 18.2 (7.8)% for the MDI and 20.9 (7.8)% and 18.9 (9.1)% for the MDI with spacer.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available