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Title: Drug metabolism in human liver
Author: Fry, Jeffrey R.
ISNI:       0000 0001 3484 9051
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1974
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The phenomenon of species differences in drug metabolism and toxicity is in many instances dependent on the ability of the liver to handle the drug in question. This problem is particularly important when attempting to extrapolate metabolism and toxicity data from laboratory animal species to man. In an effort to establish test systems that would enable this extrapolation to be predicted more reliably and accurately two different but inter-linked approaches were adopted. Firstly, isolated fractions of adult human liver were investigated. The obtention of small amounts of fresh biopsy tissue and of larger samples of post-mortem material necessitated a thorough assessment of the techniques suitable for speedy, small-scale analysis of microsomal drug metabolizing system components together with a study into the storage and post-mortem stabilities of this system. By use of these techniques large species differences in the ability of microsomes to bind drugs were noted which appeared to be related to differences in metabolism. The second approach used was that of tissue culture of adult rat hepatocytes. Once again a thorough examination of the available methods of liver culture had to be made and based on these findings a suitable culture system was devised. The cells present in culture were subjected to a battery of tests designed to show liver-specific functions. These tests proved that the epitheliocytes present in monolayer culture were in fact functional adult rat hepatocytes, a situation which appears to have been rarely, if ever, achieved previously.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available