Some drugs, administered to humans, have the capacity to induce the production of enzymes in much larger amounts than normally. The enzyme induction capacity is determined in pharmacological studies since it can represent either a benefit or a potential danger for the tested drug. In humans, induction processes can be explored using different exogenous or endogenous substances. These last compounds such as plasma gamma glutamyltransferase, urinary glucaric acid or urinary 6 beta-hydroxycortisol are particularly interesting. 6 beta-hydroxycortisol is a polar, unconjugated metabolite of cortisol which is dependent on the cytochrome P-450IIIA3 activity. Its urinary excretion is considered as a good test to evaluate inductive effects of drugs in humans and has been demonstrated to be clearly increased in subjects treated by inducers such as phenobarbital or rifampicin.
The project consists of an interlaboratory study of urinary 6 beta-hydroxycortisol determination, using an immunoenzymatic technique (ELISA) more rapid and more sensitive than other existing methods. High performance liquid chromatography (HPLC) will be used as a "reference method". It is probable that a reference material adapted to the immunoenzymatic method will be considered in the future.
The project started in July 1990. The results of a first intercomparison of measurements of urinary 6 beta-hydroxycortisol yielded a satisfactory analytical variation (4-12% day to day coefficient of variation) for ELISA method. However significant differences were observed between the results obtained by ELISA and HPLC respectively. Additional work for method comparison was recommended.
Funding SchemeCSC - Cost-sharing contracts
B15 2TT Birmingham