Comparability of in vitro and in vivo methods for the determination of alterations in drug metabolism.

The above series of experiments taken in toto suggest the usefulness of lindane as a model substrate for studying the effects of a variety of compounds on drug metabolism in vivo. Excellent correlations were observed in comparison with the in vitro measurements both qualitatively and quantitatively. Unlike some of the other compounds discussed lindane offers some distinct advantages. One is that because the metabolites can be monitored in the urine, it is non-invasive in nature. A second is that a number of mixed function oxidase pathways (phase I reactions) can be determined at the same time. This would be of great importance if the effect of a compound is rather selective and does not alter the single pathway measured in the metabolism of other substrates which have been suggested as model compounds. However, the tradeoff is obviously the need for more analytical work. A third advantage is the ability of the system to detect changes in conjugative or phase II reactions at the same time. Further studies will be necessary with all of these model substrates to detect their usefulness and their limitations.