International Eurasian Conference on Biotechnology and Biochemistry, Ankara, Türkiye, 16 - 18 Aralık 2020, ss.131
Dexamethasone, which is a synthetic glucocorticoid with anti-inflammatory and immunosuppressant effects, is used a wide range of dose for different indications. It modulates both P-gp and CYP3A4, which plays an important role in drug-drug/drug-food interactions.
We investigated the effect of different doses of dexamethasone on the expressions and functions of P-gp and CYP3A using P-gp and CYP3A substrates. A total of 54 mice were divided into 9 groups in the study. The first group was considered as the control group. Animals in groups 2, 3, 4 and 5 received low dose dexamethasone (5 mg/kg, IP), high dose dexamethasone (50 mg/kg, IP), fexofenadine (40 mg/kg, PO) and midazolam (20 mg/kg, IP), respectively. Animals in groups 6 and 7 were administered fexofenadine (40 mg/kg, PO) and midazolam (20 mg/kg, IP), 24 hours after low dose dexamethasone (5 mg/kg, IP) administration, respectively. Animals in groups 8 and 9 received fexofenadine (40 mg/kg, PO) and midazolam (20 mg/kg, IP), 24 hours after high dose dexamethasone (50 mg/kg, IP) administration, respectively. The mdr1a/b and CYP3A11/13 expressions in the liver and small intestine were determined by RT-PCR. The plasma concentrations of drugs were determined using HPLC-UV.
It can be indicated that while the effect of dexamethasone on P-gp expression is not dose-dependent, its effect on CYP3A11 is dose-dependent. Midazolam, CYP3A substrate, causes to induction of P-gp in the liver but not in the small intestine, and the effect of dexamethasone on CYP3A11 expression in the intestines was reduced by fexofenadine and midazolam.