Effects of capsicine on rat cytochrome P450 isoforms CYP1A2, CYP2C19, and CYP3A4

Drug Dev Ind Pharm. 2015;41(11):1824-8. doi: 10.3109/03639045.2015.1011166. Epub 2015 Feb 13.

Abstract

Due to the frequent consumption of capsaicin (CAP) and its current therapeutic application, the correct assessment of this compound is important from a public health standpoint. The purpose of this study was to find out whether CAP affects rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C19, and CYP3A4) by using cocktail probe drugs in vivo. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (15 mg/kg), omeprazole (15 mg/kg), and midazolam (10 mg/kg), was given orally to rats treated for 7 d with oral administration of CAP. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS. The results showed that treatment with multiple doses of CAP had no significant effect on rat CYP1A2. However, CAP had a significant inhibitory effect on CYP2C19 and an inductive effect on CYP3A4. Therefore, caution is needed when CAP is co-administered with some CYP substrates clinically because of potential drug-CAP interactions.

Keywords: CYP; Capsaicin; cocktail; drug–CAP interaction.

MeSH terms

  • Administration, Oral
  • Animals
  • Capsaicin / pharmacology*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2C19 / drug effects*
  • Cytochrome P-450 CYP2C19 / metabolism
  • Cytochrome P-450 CYP2C19 Inhibitors / pharmacology
  • Cytochrome P-450 CYP3A / drug effects*
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inducers / pharmacology
  • Cytochromes / drug effects*
  • Cytochromes / metabolism
  • Drug Interactions
  • Male
  • Mass Spectrometry
  • Midazolam / metabolism
  • Omeprazole / metabolism
  • Phenacetin / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cytochrome P-450 CYP2C19 Inhibitors
  • Cytochrome P-450 CYP3A Inducers
  • Cytochromes
  • Cyp1a2 protein, rat
  • Cyp3a2 protein, rat
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP3A
  • Phenacetin
  • Omeprazole
  • Midazolam
  • Capsaicin