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MARÍA JOSÉ GÓMEZ-LECHÓN y MARÍA TERESA DONATO AN. R. ACAD. NAC. FARM.

is highly induced by different groups of compounds, including
therapeutic agents such as glucocorticoids, antibiotics,
anticonvulsants, or anti-inflammatories (14, 70-72).

The use of in vitro models able to reflect interindividual variations
in drug metabolism will notably increase the relevance of preclinical
metabolic studies. The analysis of P450 enzymes in microsomes from
a human liver bank revealed the existence of considerable variability
(73). As an example, high variations (>50-fold) were found in CYP3A4
activity levels in microsome preparations form 30 different livers
(Figure 5A). A similar picture is observed when CYP3A4 activity is
measured in primary human hepatocyte cultures prepared from
different donors (Figure 5B). Incubation of the compound of interest
with human liver microsomes or hepatocytes expressing different
levels of P450 enzymes will help to anticipate information on

FIGURE 5. Variability of CYP3A4 activity in human liver and human
hepatocytes from different donors. CYP3A4 activity (testosterone

6ß-hydroxylation) was determined (A) in microsomes from a human liver bank
(n = 30), and (B) in different preparations of human hepatocytes. The individual

data for CYP3A4 activity are plotted and sorted in decreasing order to show
inter-individual variability.

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