[Variation in the urinary excretion of 6-beta-hydroxycortisol in humans after administration of the new isoquinoline derivative, PK-11195 (52028 RP)].
Among in vivo tests to assess liver drug metabolizing enzyme induction, urinary 6-beta-hydroxycortisol (6-beta-OHF), plasma gamma-glutamyltransferase (GGT) and urinary D-glucaric acid are most frequently proposed. 6-beta-OHF is the most abundant unconjugated metabolite of cortisol in human urine. We measured its elimination during a clinical trial in 16 human healthy volunteers (men and women), these persons being treated by a new isoquinoleine derivative, 52028 RP (PK-11195). This drug is an antagonist of peripheral type benzodiazepine binding sites. Urinary excretion of 6-beta-OHF increased significantly (3.5 fold, p less than 0.01) on the 5th day of treatment (400 mg/day, orally) and remained increased as long as the treatment was continued (15 days). Control values were again observed 5 days after stopping the treatment. Plasma gamma-glutamyltransferase activity and D-glucaric acid urinary elimination are increased more than 2 fold. The data demonstrated that 6-beta-OHF in the most sensitive among the three tests performed to detect a drug metabolism induction, during this clinical trial.
Freche
J P
JP
Decolin
D
D
Siest
J P
JP
Batt
A M
AM
Panis-Rouzier
R
R
Siest
G
G
D000328:Adult; D002986:Clinical Trials as Topic; D005260:Female; D005937:Glucaric Acid / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D007546:Isoquinolines / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D012016:Reference Values; D005723:gamma-Glutamyltransferase / Q000097:blood
D007546:Isoquinolines; C001380:6 beta-hydroxycortisol; D005723:gamma-Glutamyltransferase; D005937:Glucaric Acid; D006854:Hydrocortisone; C037850:PK 11195
Variation chez l'homme de l'excrétion du 6-beta-hydroxycortisol urinaire après administration d'un nouveau dérivé de l'isoquinoléine, PK-11195 (52028 RP).