PURPOSE: The objective of this investigation was to assess whether common pharmaceutical excipients regulate the expression of drug-metabolizing enzymes in human colon and liver cells. METHODS: Nineteen commonly used excipients were evaluated using a panel of experiments including cell-based human PXR activation assays, real-time RT-PCR assays for CYP3A4 mRNA expression, and immunoblot analysis of CYP3A4 protein expression in immortalized human liver cells (HepG2 and Fa2N4), human primary hepatocytes, and the intestinal LS174T cell models. RESULTS: No excipient activated human PXR or practically induced CYP3A4. However, three excipients (polysorbate 80, pregelatinized starch, and hydroxypropyl methylcellulose) tended to decrease mRNA and protein expression across experimental models. CONCLUSION: This study represents the first investigation of the potential role of excipients in the expression of drug-metabolizing enzymes. Findings imply that some excipients may hold potential for excipient-drug interactions by repression of CYP3A4 expression.
PURPOSE: The objective of this investigation was to assess whether common pharmaceutical excipients regulate the expression of drug-metabolizing enzymes in human colon and liver cells. METHODS: Nineteen commonly used excipients were evaluated using a panel of experiments including cell-based humanPXR activation assays, real-time RT-PCR assays for CYP3A4 mRNA expression, and immunoblot analysis of CYP3A4 protein expression in immortalized human liver cells (HepG2 and Fa2N4), human primary hepatocytes, and the intestinal LS174T cell models. RESULTS: No excipient activated humanPXR or practically induced CYP3A4. However, three excipients (polysorbate 80, pregelatinized starch, and hydroxypropyl methylcellulose) tended to decrease mRNA and protein expression across experimental models. CONCLUSION: This study represents the first investigation of the potential role of excipients in the expression of drug-metabolizing enzymes. Findings imply that some excipients may hold potential for excipient-drug interactions by repression of CYP3A4expression.
Authors: S A Kliewer; J T Moore; L Wade; J L Staudinger; M A Watson; S A Jones; D D McKee; B B Oliver; T M Willson; R H Zetterström; T Perlmann; J M Lehmann Journal: Cell Date: 1998-01-09 Impact factor: 41.582
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Authors: Sharmila Das; Dong Guo; Xiaohui Jiang; Wenlei Jiang; Yan Shu; Tricia Y Ting; James E Polli Journal: Pharm Res Date: 2020-02-26 Impact factor: 4.200