A sensitive, specific and rapid HPLC procedure was developed in order to monitor plasma levels of simvastatin (MK-733), a novel and potent competitive inhibitor of 3-Hydroxymethyl-glutaryl CoA reductase, and its biologically active hydroxyacid metabolite, L-654-969. This method was applied to a series of plasma samples collected from hypercholesterolemic 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 minutes, 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 drug distribution in the body are discussed.
HPLC determination of simvastatin and L-654,969 in human plasma after oral administration of simvastatin to hypercholesterolemic patients
CARLUCCI, Giuseppe;MAZZEO, PIETRO;
1994-01-01
Abstract
A sensitive, specific and rapid HPLC procedure was developed in order to monitor plasma levels of simvastatin (MK-733), a novel and potent competitive inhibitor of 3-Hydroxymethyl-glutaryl CoA reductase, and its biologically active hydroxyacid metabolite, L-654-969. This method was applied to a series of plasma samples collected from hypercholesterolemic 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 minutes, 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 drug distribution in the body are discussed.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
