Effects of simvastatin and pravastatin on 6 beta-hydroxycortisol excretion, a potential marker of cytochrome P-450 3A

Pharmacol Res. Oct-Nov 1993;28(3):243-8. doi: 10.1006/phrs.1993.1127.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • 17-Hydroxycorticosteroids / urine
  • Adult
  • Biomarkers
  • Creatinine / urine
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 Enzyme System / metabolism*
  • Humans
  • Hydrocortisone / analogs & derivatives*
  • Hydrocortisone / urine
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Lovastatin / analogs & derivatives*
  • Lovastatin / pharmacology
  • Male
  • Mixed Function Oxygenases / metabolism*
  • Pravastatin / pharmacology*
  • Simvastatin

Substances

  • 17-Hydroxycorticosteroids
  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • 6 beta-hydroxycortisol
  • Cytochrome P-450 Enzyme System
  • Lovastatin
  • Simvastatin
  • Creatinine
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2E1
  • Pravastatin
  • Hydrocortisone