title: Effects of commonly used excipients on the expression of CYP3A4 in colon and liver cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, Maryland 21201, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Tompkins
authors.forename: Caitlin
authors.initials: C
authors.lastname: Lynch
authors.forename: Sam
authors.initials: S
authors.lastname: Haidar
authors.forename: James
authors.initials: J
authors.lastname: Polli
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
mesh_terms: D003106:Colon / Q000166:cytology* / Q000187:drug effects*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D005079:Excipients / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005079:Excipients; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human