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Title: A development of some simple measures for assessing gastrointestinal transit in clinical pharmacology, with special reference to variability and validity
Author: Staniforth, David Harold
ISNI:       0000 0001 3477 3202
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1997
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Section 1: The Lactulose breath hydrogen method of assessing orocolonic transit time is investigated with reference to Variability and Validity. Experiments were designed to quantify this variability with standardised end point, meal composition and patient position. The data is analysed so that statistically meaningful results can be obtained when using the method as a tool in Clinical Pharmacology. A similar study using the bean breath hydrogen method is undertaken. The Validity of the Lactulose breath hydrogen method was investigated radiologically to ascertain the anatomical nature of the transit time measured. The Sulphasalazine sulphapyridine method, also gut bacteria, dependent, was selected for development. By implementing an HPLC assay for Sulphapyridine a more precise answer was obtained. The Variability of the transit time measured with the developed method is quantified and predictions made as to the number of patients that would be required to take part in studies if meaningful statistical results are to be obtained. Section 2: The two methods developed for assessing Oro Colonic transit time are used to evaluate the potency of some substituted Benzamides and their potency ratio, with confidence interval, relative to metoclopramide is calculated. The significance of 5-HT receptor specificity in relation to upper and lower bowel action is investigated. Section 3: Methods of investigating the action of New Chemical Entities on Gastric emptying is discussed. The paracetamol method was selected for further development by: a) Implementing an assay using an enzymatic technique. b) Carrying out a detailed pharmacokinetic study of intravenous paracetamol to provide data for calculating the amount of paracetamol absorbed using Loo Riegelman absorption time plots as an indirect measure of gastric emptying. The modified technique was validated by comparing it with Applied Potential Tomography; another measure of gastric emptying.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Gastric emptying; Oro colonic transit time