Effects of simvastatin and pravastatin on 6 beta-hydroxycortisol excretion, a potential marker of cytochrome P-450 3A.
The influence of two inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, simvastatin and pravastatin, on the level of urinary 6 beta-hydroxycortisol/17-hydroxycorticosteroids (6 beta-OHC/17-OHCS) ratio was determined in two groups of normolipidemic Caucasian subjects (n = 18 and n = 14, respectively). The 6 beta-OHC/17-OHCS ratio increased significantly after simvastatin administration (20 mg day-1 for 17 days) (P = 0.0125) whereas no modification was observed after pravastatin administration (20 mg day-1 during 17 days). As the level of 6 beta-OHC/17-OHCS ratio is a function of cytochrome P-450 3A activity, these results suggest that in Caucasian subjects, simvastatin but not pravastatin could be a weak inducer of cytochrome P-450 3A. This contrasting effect could be related to the major pharmacological differences existing between these two drugs.
Horsmans
Y
Y
Laboratoire de Pharmacothérapie, Université Catholique de Louvain, Bruxelles, Belgium.
Desager
J P
JP
van den Berge
V
V
Abrassart
M
M
Harvengt
C
C
D015065:17-Hydroxycorticosteroids / Q000652:urine; D000328:Adult; D015415:Biomarkers; D003404:Creatinine / Q000652:urine; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D017035:Pravastatin / Q000494:pharmacology*; D019821:Simvastatin
D015065:17-Hydroxycorticosteroids; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; D008148:Lovastatin; D019821:Simvastatin; D003404:Creatinine; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D017035:Pravastatin; D006854:Hydrocortisone