Fig. 6.
Effect of berberine on the metabolite ratio for MDZ hydroxylation (i.e., 1′-OH/4-OH-MDZ) produced by HLMs or CYP3A4 or CYP3A5 Supersomes. Metabolite ratios were highest at the lowest concentrations of substrate tested and decreased markedly at concentrations exceeding the Km for MDZ 4-hydroxylation (∼12–25 μM). When berberine was added as effector, an increase in the maximum metabolite ratio was observed with all three enzyme sources; however, this increase was modest for CYP3A4 (1.35–1.6-fold at 100 μM berberine) compared with CYP3A5 (∼30-fold), whereas the 3.5-fold increase in the maximum metabolite ratio produced by berberine in HLMs lay in between these values.