title: [Variation in the urinary excretion of 6-beta-hydroxycortisol in humans after administration of the new isoquinoline derivative, PK-11195 (52028 RP)].
abstract: 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.
authors.forename: J P
authors.initials: JP
authors.lastname: Freche
authors.forename: D
authors.initials: D
authors.lastname: Decolin
authors.forename: J P
authors.initials: JP
authors.lastname: Siest
authors.forename: A M
authors.initials: AM
authors.lastname: Batt
authors.forename: R
authors.initials: R
authors.lastname: Panis-Rouzier
authors.forename: G
authors.initials: G
authors.lastname: Siest
mesh_terms: 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
chemical_list: D007546:Isoquinolines; C001380:6 beta-hydroxycortisol; D005723:gamma-Glutamyltransferase; D005937:Glucaric Acid; D006854:Hydrocortisone; C037850:PK 11195
vernacular_title: 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).