HPLC DETERMINATION OF SIMVASTATIN AND L-654,969 IN HUMAN PLASMA AFTERORAL-ADMINISTRATION OF SIMVASTATIN TO HYPERCHOLESTEROLEMIC PATIENTS

A sensitive, specific and rapid HPLC procedure was developed in order to monitor plasma levels of simvastatin (MK-733), a novel and potent c ompetitive inhibitor of 3-Hydroxymethyl-glutaryl CoA reductase, and it s biologically active hydroxyacid metabolite, L-654-969. This method w as applied to a series of plasma samples collected from hypercholester olemic patients (n=10) at various times after a single 10 mg oral dose of simvastatin. A peak plasma level of simvastatin was observed at 30 minutes and peak levels of its major metabolite were observed at 60 m inutes, with disappearance of these chemicals within 8-24 hours after the administration. Clinical and experimental relevance of this method for the pharmacokinetic assessment and the organ specificity of the d rug distribution in the body are discussed.