P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) play a significant role in the disposition and elimination of drugs. The objective of this study was to investigate the mechanism underlying the interaction between sitagliptin (substrate of P-gp and CYP3A4) and verapamil (known modulator of P-gp and CYP3A4) using in vivo, ex vivo and in situ models. Rats were treated with sitagliptin (10 m...

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to induce the expression of cytochrome P450 3A4 (CYP3A4) in human colon carcinoma Caco-2 cells. Recently, it was demonstrated that the vitamin D receptor (VDR) regulates 1,25(OH)2D3-induced CYP3A4 gene expression through the xenobiotic-responsive element and the vitamin D-responsive element located on the 5 -flanking region of the CYP3A4 gene. On ...

Objective: To evaluate the effect of NIPRD-AM1 on CYP3A4 in order to generate clinically significant data for its safe and efficacious use. Materials and Methods: NIPRD-AM1 is a phytomedicine developed from aqueous root extracts of Nauclea latifolia Smith (Rubiaceae) for the treatment of uncomplicated malaria. The effect of NIPRD-AM1 on CYP3A4 was measured with and without the addition of NIPRD...

Introduction: Amiodarone is one of drug with narrow therapeutics index. This medicine was metabolized by CYP3A4 and CYP2C8. The changes in the activity this enzymes CYP2C8 polymorphism will affect effect. study aimed to determine impact on amiodarone responses. Method: review article search PubMed keywords: ‘amiodarone’ ‘polymorphism CYP3A4’ CYP2C8’. Results: We collect 46 references Conclusion...

Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, c...

Pregnane X receptor (PXR) has been shown to form a heterodimer with retinoid X receptor alpha (RXRalpha) and to bind to the distal nuclear receptor-binding element 1 and an everted repeat separated by six nucleotides in the proximal promoter of the CYP3A4 gene. In the present study, a new rifampicin-responsive region, located at -7.6 kilobases upstream from the transcription initiation site, ha...

Cytochrome P450 3A4 (CYP3A4) is the major cytochrome P450 present in adult human liver and is involved in the metabolism of over 50% of therapeutic compounds currently in use. Since expression levels of CYP3A4 are regulated by many of these compounds, this raises the potential for drug-drug interactions and subsequent altered efficacy or toxicity of the individual compounds at the dose prescrib...

Variations in the expression of human pregnane X receptor (hPXR)– mediated cytochrome p450 3A4 (CYP3A4) in liver can alter therapeutic response to a variety of drugs and may lead to potential adverse drug interactions. We sought to determine whether Mg/Mndependent phosphatase 1A (PPM1A) regulates hPXR-mediated CYP3A4 expression. PPM1A was found to be coimmunoprecipitated with hPXR. Genetic or p...

The balance between bioactivation and degradation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is critical for ensuring appropriate biological effects of vitamin D. Cytochrome P450, family 24-mediated (CYP24-mediated) 24-hydroxylation of 1,25(OH)2D3 is an important step in the catabolism of 1,25(OH)2D3. The enzyme is directly regulated by vitamin D receptor (VDR), and it is expressed mainly in the...