![]() ![]() There was a marked interindividual variability in the grapefruit juice–simvastatin interaction, e.g. The present study shows that even once daily consumption of a glass of grapefruit juice considerably increases plasma concentrations of simvastatin. The present study was conducted to investigate the effect of a single daily glass of grapefruit juice on the pharmacokinetics of simvastatin and its active metabolite, simvastatin acid. In a previous study a daily volume of 250 ml of grapefruit juice had a modest effect on lovastatin, but in that study grapefruit juice had been taken about 12 h apart from statin. Repeated consumption of high quantities of grapefruit juice has increased the AUC values of lovastatin and simvastatin over 10-fold. Grapefruit juice has increased plasma concentrations of dihydropyridine calcium channel blockers, cyclosporin, midazolam, and some HMG-CoA reductase inhibitors, probably by a selective downregulation of CYP3A4 at duodenal epithelium where CYP3A4 is localized. erythromycin, diltiazem and itraconazole, that increase plasma concentrations of simvastatin and simvastatin acid. Thus, myopathies and even rhabdomyolysis with acute renal failure have been associated with simultaneous use of simvastatin with CYP3A4 inhibitors, e.g. However, high plasma concentrations increase the risk of musculoskeletal adverse effects. Some of the metabolites of simvastatin also show pharmacological activity. Because of the extensive CYP3A4-mediated metabolism already during the first pass, simvastatin has a low mean oral bioavailability of about 5%. In the other primary route the inactive lactone prodrug is hydrolysed to the pharmacologically active simvastatin acid by carboxyl esterases and also non-enzymatically. The oxidative biotransformation of simvastatin is mediated primarily by CYP3A4. Simvastatin, an HMG-CoA reductase inhibitor, is widely used in the treatment of hypercholesterolaemia. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |