Whole Zebrafish Cytochrome P450 Assay for Assessing Drug Metabolism and Safety - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 107

Table 9.1 CYP3A4 Inhibition in Zebrafish: IC 50 Values

CYP3A4 inhibitors CYP3A4 inhibition IC 50 values in zebrafish (mM)

Azamulin 187.3

Disopyramide 123.1

Erythromycin 128.9

Fluvoxamine 42.7

Omeprazole 10.2

Cimetidine 80.2

IC 50 values (the concentration at which 50% CYP3A4 inhibition is observed) are
summarized in Table 9.1.
Four of the six human CYP3A4 inducers (prednisone, hydrocortisone, carba-
mazepine, and pregnenolone-16 -carbonitrile) increased zebrafish CYP3A4 func-

tional activity. Percent increase in induction compared to 0.1% DMSO control was
111-126% for carbamazepine, 119-139% for hydrocortisone, 122% for prednisone,
and 123-135% for pregnenolone-16

a

-carbonitrile; human CYP3A4 inducers lova-
statin and phenytoin did not affect zebrafish CYP3A4 functional activity (Fig. 9.4).
EC 50 values (the concentration at which 50% CYP3A4 induction was observed) are
summarized in Table 9.2.

a

Figure 9.4 CYP3A4 induction using microplate-based whole zebrafish CYP3A4 assay. Two dpf
zebrafish were treated with CYP3A4 inducers for 24 h and zebrafish CYP3A4 activities were
measured using a CYP3A4 chemiluminogenic substrate. Zebrafish treated with 0.1% DMSO (vehicle)
were used as a negative control and zebrafish treated with 50 mM dexamethasone (Dex) served as a
positive control. Data are expressed as mean SD. p < 0.05, p < 0.01, and p <

0.001 compared with
0.1% DMSO control. Phenytoin and lovastatin did not cause significant effects on CYP3A4 activity
in zebrafish.