 All statins are (metabolized) by the liver, which causes their low systemic bioavailability.Lovastatin and simvastatin are administered in their lactone forms, which is more lipophilic than their free acid forms, and therefore they have to be activated by hydrolysis to the active anionic carboxylate form.Cytochrome P450(CYP) isoenzymes are involved in the oxidative metabolism of the statins, with CYP3A4 and CYP2C9 isoenzymes being the most dominant.