Absence of CYP3A genetic polymorphism assessed by urinary excretion of 6 beta-hydroxycortisol in 102 healthy subjects on rifampicin.
A previous study has demonstrated that the urinary level of 6 beta-hydroxycortisol is a marker of liver CYP3A content after induction by rifampicin. To put in evidence an eventual genetic polymorphism for this cytochrome, the frequency distribution of 6 beta-hydroxycortisol excretion was investigated in 102 healthy Caucasians before and after 6 days of oral rifampicin administration (600 mg daily). After rifampicin treatment, a wide interindividual distribution was observed but no clear bimodality. Moreover the mean 6 beta-hydroxycortisol level was higher in women (n = 38) than in men (n = 64). These observations do not favour the existence of a CYP3A genetic polymorphism based on 6 beta-hydroxycortisol excretion but evoke a sexual dimorphism. However, CYP3A is composed of at least four enzymes and as the enzyme(s) responsible for cortisol 6 beta-hydroxylation is (are) not perfectly known, it can not be excluded that a genetic polymorphism does exist for one enzyme of this family.
Horsmans
Y
Y
Laboratory of Pharmacotherapy, Catholic University of Louvain, Bruxelles, Belgium.
Desager
J P
JP
Harvengt
C
C
D015065:17-Hydroxycorticosteroids / Q000652:urine; D000284:Administration, Oral; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012293:Rifampin / Q000494:pharmacology*
D015065:17-Hydroxycorticosteroids; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D012293:Rifampin; D006854:Hydrocortisone