Rosuvastatin is a selective and competitive inhibitor of HMG-CoA reductase, the
rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to
mevalonate, a precursor for cholesterol. The primary site of action of rosuvastatin is
the liver, the target organ for cholesterol lowering.
- Rosuvastatin increases the number of hepatic LDL receptors on the cell-surface,
enhancing uptake and catabolism of LDL and it inhibits the hepatic synthesis of
VLDL, thereby reducing the total number of VLDL and LDL particles.
- Maximum rosuvastatin plasma concentrations are achieved approximately 5 hours
after oral administration. The absolute bioavailability is approximately 20%.
- Rosuvastatin undergoes limited metabolism (approximately 10%). In vitro metabol-
ism studies using human hepatocytes indicate that rosuvastatin is a poor substrate
for cytochrome P450-based metabolism. The main metabolites identified are the
N-desmethyl and lactone metabolites. The N-desmethyl metabolite is approximat-
ely 50% less active than rosuvastatin whereas the lactone form is considered clini-
cally inactive. Rosuvastatin accounts for greater than 90% of the circulating
HMG-CoA reductase inhibitor activity.
- Approximately 90% of the rosuvastatin dose is excreted unchanged in the faeces
(consisting of absorbed and non-absorbed active substance) and the remaining part
is excreted in urine. The plasma elimination half-life is approximately 19 hours.