Expression and Induction of Drug-Metabolizing Enzymes in Cultured Fetal Rat Hepatocytes

An in vitro experimental model, fetal rat hepatocytes in culture, was metabolically characterized. Several enzymatic activities were expressed in these hepatocytes, namely, testosterone hydroxylations. Hepatocytes cultured up to 3 weeks in the presence of dexamethasone and phenobarbital still expressed some drug-metabolizing enzyme activities (e.g., ECOD). The enzymatic activities were measured both directly on monolayers during culture and on the corresponding harvested and homogenized cells. The results correlate perfectly with each other. The 'on cell' procedure allows us to repeat the assay or to measure several activities on the same cells at different time intervals. The presence of dexamethasone in the culture medium allows the expression and the induction of several cytochrome P450 isoenzymes, namely, those hydroxylating testosterone. This makes the model particularly attractive for induction experiments as well as for metabolic or toxicological studies needing longer treatments

Model reduction of large-scale systems: rational Krylov versus balancing techniques

In this paper, we describe some recent developments in the use of projection methods to produce a reduced-order model for a linear timeinvariant dynamical system which approximates its frequency response. We give an overview of the family of Rational Krylov methods and compare them with "near-optimal" approximation methods based on balancing transformations