title: In-vitro inhibitory effect of Tualang honey on cytochrome P450 2C8 activity.
abstract: OBJECTIVE
  To investigate the effect of Tualang honey on cytochrome P450 2C8 (CYP2C8) activity in vitro using an amodiaquine N-desethylase assay.
  
  
  METHODS
  CYP2C8 and NADPH cytochrome P450 reductase was cotransformed, expressed and harvested. The incubation assay contained expressed proteins, MgCl(2), NADP, glucose 6-phosphate, glucose-6-phosphate dehydrogenase, potassium phosphate buffer, and amodiaquine. The rate of conversion of amodiaquine to desethylamodiaquine, the metabolite, was determined using a high performance liquid chromatography (HPLC) method. The inhibition parameters, IC50 (concentration of inhibitor causing 50% inhibition of original enzyme activity) and apparent inhibition constant (K(i) ) values were determined.
  
  
  RESULTS
  The recombinant proteins were successfully expressed and used to investigate the effect of Tualang honey on CYP2C8 activity. The activity was measured by the rate of metabolism of amodiaquine to desethylamodiaquine determined using a successfully developed HPLC method. Kinetic parameters as determined by nonlinear least-squares regression and evaluated with Aikeike's goodness of fit criteria revealed that Tualang honey competitively inhibited CYP2C8 activity in a dose-dependent manner. Maximum inhibition of 80% occurred at 0.01% honey. The IC50 and K(i) values were (10.0 ± 3.0) × 10(-3) % and (5.1 ± 0.5) × 10(-3) % w/v, respectively.
  
  
  CONCLUSIONS
  This study has provided evidence for the in vitro inhibition of CYP2C8-mediated amodiaquine N-desethylase activity by Tualang honey. It revealed that honey, through this inhibition, may have the potential to cause in-vivo drug-food interaction with drugs metabolized by CYP2C8.
authors.affiliation: Pharmacogenetics & Novel Therapeutics Cluster, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Yasotha Devi
authors.initials: YD
authors.lastname: Muthiah
authors.forename: Chin Eng
authors.initials: CE
authors.lastname: Ong
authors.forename: Siti Amrah
authors.initials: SA
authors.lastname: Sulaiman
authors.forename: Soo Choon
authors.initials: SC
authors.lastname: Tan
authors.forename: Rusli
authors.initials: R
authors.lastname: Ismail
mesh_terms: D000655:Amodiaquine / Q000031:analogs & derivatives / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D002851:Chromatography, High Pressure Liquid; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D018565:Food-Drug Interactions; D006722:Honey; D020128:Inhibitory Concentration 50; D007700:Kinetics; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D011994:Recombinant Proteins; D000655:Amodiaquine; C047386:desethylamodiaquine; D001189:Aryl Hydrocarbon Hydroxylases