Effect of honey on CYP3A4, CYP2D6 and CYP2C19 enzyme activity in healthy human volunteers.
Honey is a common food supplement but not many studies have studied honey and drug interaction. This study investigates the influence of 7 days of honey administration on the activity of CYP3A4, CYP2D6 and CYP2C19 drug-metabolizing enzymes in healthy volunteers by using appropriate biomarker and probe drugs. A within-group pharmacokinetic study was done in 12 healthy volunteers. Urine samples (0-8 hr) were collected after administration of 30 mg of oral dextromethorphan (probe drug for CYP2D6) for analysis of dextromethorphan and dextrorphan. A plasma sample (4 hr) was collected after administration of 200 mg of oral proguanil (probe drug for CYP2C19) for the analysis of proguanil and cycloguanil. Urine samples (0-24 hr) were collected for the analysis of 6beta-hydroxycortisol (biomarker for CYP3A4). The volunteers were administered honey for 7 days. Subsequently blood and urine samples were collected after drug dosing as before. These samples were analysed for drug and metabolite concentrations in urine and plasma using high performance liquid chromatography method. Seven days of honey administration resulted in statistically significant increase in 24-hr urinary excretion of 6beta-hydroxycortisol. However, the metabolic ratios of dextromethorphan and proguanil were not significantly altered after 7 days of honey administration. Honey obtained from Western Ghats of southern India may induce CYP3A4 enzyme activity but not CYP2D6 and CYP2C19 enzyme activities.
Tushar
Tewari
T
Department of Pharmacology, Jawaharlal Institute of Post-graduate Medical Education and Research, Pondicherry, India.
Vinod
Thomas
T
Rajan
Sundaram
S
Shashindran
Chanolean
C
Adithan
Chandrasekaran
C
D000284:Administration, Oral; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003915:Dextromethorphan / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D003917:Dextrorphan / Q000097:blood; D006722:Honey; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D007194:India; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D002727:Proguanil / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D014227:Triazines / Q000652:urine
D014227:Triazines; D003917:Dextrorphan; C026009:cycloguanil; C001380:6 beta-hydroxycortisol; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D002727:Proguanil; D006854:Hydrocortisone