Pharmacokinetics and drug metabolism
Absorption: In clinical pharmacology studies in man, peak plasma concentrations of
rosuvastatin were reached 3 to 5 hours following oral dosing. Both peak concentration (Cmax)
and area under the plasma concentration-time curve (AUC) increased in approximate proportion
to rosuvastatin dose. The absolute bioavailability of rosuvastatin is approximately 20%.
Administration of rosuvastatin with food decreased the rate of drug absorption by 20% as
assessed by Cmax, but there was no effect on the extent of absorption as assessed by AUC.
Plasma concentrations of rosuvastatin do not differ following evening or morning drug
administration.
Significant LDL-C reductions are seen when rosuvastatin is given with or without food, and
regardless of the time of day of drug administration.
Distribution: Mean volume of distribution at steady-state of rosuvastatin is approximately 134
liters. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible
and independent of plasma concentrations.
Metabolism: Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled
dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which is
formed principally by cytochrome P450 2C9, and in vitro studies have demonstrated that
N-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG-CoA reductase
inhibitory activity of rosuvastatin. Overall, greater than 90% of active plasma HMG-CoA
reductase inhibitory activity is accounted for by rosuvastatin.
Excretion: Following oral administration, rosuvastatin and its metabolites are primarily
excreted in the feces (90%). The elimination half-life (t1/2) of rosuvastatin is approximately 19
hours.
After an intravenous dose, approximately 28% of total body clearance was via the renal route,
and 72% by the hepatic route.