Effect of grapefruit juice on urinary 6 beta-hydroxycortisol/cortisol excretion.
1. The aim of the present study was to evaluate the effect of grapefruit juice on urinary 6 beta-hydroxycortisol and cortisol excretion in healthy subjects. 2. The ratio of 6 beta-hydroxycortisol/cortisol was significantly decreased (P = 0.036) in the 0-4 h fraction of urine after ingestion of grapefruit juice, but not in the 4-24 h fraction (P = 0.218) or for the compiled data, fraction 0-24 h (P = 0.114). 3. These results indicate that endogenous cortisol metabolism may not only be of hepatic origin, but may also be dependent on the metabolic capacity of cytochrome P450 IIIA (CYP3A) in the gut mucosa. 4. This finding may cast further doubts of the usefulness of the 6 beta-hydroxycortisol/cortisol ratio as an indicator of hepatic CYP3A activity.
Seidegård
J
J
Department of Human Pharmacology, Astra Draco AB, Lund, Sweden. Janeric.Seidegard@draco.se.astra.con
Dahlström
K
K
Kullberg
A
A
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001628:Beverages; D002957:Citrus / Q000378:metabolism*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine*; D008099:Liver / Q000201:enzymology; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*
C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D006854:Hydrocortisone