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• W2566129960 abstract "1. Present investigation was carried out in rats to study influence of corticosteroids after repeated dosing with/without pre-treatment with CYP2D inhibitor quinidine on the CYP2D1 mRNA levels and CYP2D enzyme activity using dextromethorphan as probe substrate.2. CYP2D1 mRNA was measured in liver homogenate using quantitative real-time polymerase chain reaction [qRT-PCR] and enzymatic reaction was studied ex vivo in liver S-9 fractions of rats treated with oral 10 mg/kg dexamethasone or prednisolone for five days or pre-treated with quinidine and followed by treatment with oral 10 mg/kg corticosteroids for five days.3. Five days repeat dosing of dexamethasone or prednisolone decreased the activity of the rat liver CYP2D by 37% and 34%, at 30 min incubation and decreased CYP2D1 mRNA levels by 62% and 61%, respectively.4. Pre-treatment of quinidine decreased the enzymatic activity of rat CYP2D by 58% and did not potentiate CYP2D inhibition by corticosteroids. This observation was further complemented by qRT-PCR data.5. Corticosteroids caused CYP2D inhibition in rats vs. literature evidence of CYP2D induction in human hepatocytes/pregnant humans demonstrating lack of concordance. In vivo inhibition should be factored for interpretation of pharmacokinetic data of CYP2D substrates when treated with corticosteroids in rats." @default.
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• W2566129960 date "2017-01-19" @default.
• W2566129960 modified "2023-10-16" @default.
• W2566129960 title "Consequences of daily corticosteroid dosing with or without pre-treatment with quinidine on the <i>in vivo</i> cytochrome P450 2D (CYP2D) enzyme in rats: effect on O-demethylation activity of dextromethorphan and expression levels of CYP2D1 mRNA" @default.
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• W2566129960 doi "https://doi.org/10.1080/00498254.2016.1275064" @default.
• W2566129960 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28010169" @default.
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