An apparatus to simulate metabolism of ingested substances.
A prototype in vitro, closed in-line apparatus was designed to simulate the passage of a substance through the gastro-intestinal tract and absorption by internal body organs with appropriate metabolism at each stage, with computer-controlled culture conditions to resemble normal in vivo physiology. In tests to define conditions of use, comparisons of tests using water-bath and metabolic simulator techniques showed formation of similar metabolites of sodium lauryl sulphate. Comparison of in vivo and in vitro results showed the advantage of the in vitro system to identify metabolites. The end-product butyric acid-4-sulphate excreted in the urine of rats after a single oral dose of [(14)C]sodium lauryl sulphate was also formed by hepatocytes in vitro in a water-bath vessel, which indicates the relevance of the intermediary metabolites detected by sequential sampling over 24 hr in the metabolic simulator. The intermediary metabolites identified were 11- and 12-hydroxy dodecyl sulphate, 12-carboxy dodecyl sulphate and probably 11-keto dodecyl sulphate. This evidence was not readily obtainable from the in vivo test. Once limitations of this prototype design are overcome, the system should enable comparison of the metabolism of test substances between species, including man, and eventually the use of laboratory-adapted cultures of relevant organs to replace primary in vivo sources of tissues.
Parish
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Environmental Safety Laboratory, Unilever Research, Colworth House, Sharnbrook, Bedford MK44 1LQ, UK.
Wood
J
J
Groger
W
W
Sharma
R K
RK