Pitalip

Pitalip Mechanism of Action

pitavastatin

Manufacturer:

Daewoong Pharmaceutical

Distributor:

Zuellig Pharma

Marketer:

Abbott
Full Prescribing Info
Action
Pharmacology: Pharmacodynamics: Pitavastatin is a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) which is the key enzyme responsible for conversion of HMG-CoA to mevalonate. This target reaction is an early rate-limiting step in cholesterol biosynthesis. By blocking this enzyme, pitavastatin markedly reduce plasma concentrations of low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) and to a lesser extent apolipoprotein B (Apo-B) and triglycerides (TGs) as well as increase levels of high density lipoprotein cholesterol (HDLC) in patients with primary hypercholesterolemia or mixed dyslipidemia.
The mechanism of LDL-C lowering action may involve both reduction of very low density lipoprotein (VLDL) synthesis and increasing of LDL-C receptors. These reactions lead to reduced production and/or increased uptake and catabolism of LDL-C. Pitavastatin is an active molecule that not requires bioactivation after oral administration. Lipid-lowering effects were seen within 1-2 weeks and maximum therapeutic efficacy occurred within 4-6 weeks. Reductions in blood LDL-C concentrations were dose-dependent.
Pharmacokinetics: Absorption: The bioavailability of pitavastatin is 51%. Pitavastatin peak plasma concentrations (Cmax) occurre at 1 hour after oral administration. Coadministration of pitavastatin and food decreased rate of pitavastatin absorption by 43%, but does not significantly reduce the extent of absorbed pitavastatin. Plasma concentration of pitavastatin is higher in elderly (approximately 30% for area under the concentration-time curve [AUC]). Rate and extent of pitavastatin absorption are increased by 60% and 79%, respectively, in patients with moderate renal impairment.
Distribution: Pitavastatin is uptaken into hepatocytes by organic anionic transport polyppeptide (OATP) 1B1, 1B3, and 2B1. Hepatic uptake of pitavastatin is required for pharmacologic effects. More than 99% of serum pitavastatin is bound to serum protein. Data regarding distribution of pitavastatin into certain tissues are limited. Pitavastatin is distributed into breast milk in rats, but unknown in human. Because of the potential serious adverse reactions in breast-feeding infants, caution women this drug not to breast-feed their infants.
Metabolism and Elimination: Pitavastatin has a unique metabolic profile compared to other statins that contributes to a longer duration of action and a higher safety profile due to less drug-drug interactions. Pitavastatin is mostly metabolized by uridine 5'-diphosphae (UDP) glucuronosyltransferase (e.g. UGT1A1, UGT1A3, and UGT2B7) to an ester-type pitavastatin glucoronide conjugate and further metabolized to the inactive pitavastatin lactone metabolite. Small proportion of pitavastatin is metabolized by cytochrome P450 (CYP) hepatic enzymes, mainly 2C9 and 2C8. Mean plasma elimination half-life of pitavastatin is approximately 12 hours. 79% or 15% of oral administered solution of pitavastatin is excreted in feces and urine, respectively, within 7 days.
Pharmacokinetics Study in Hepatic Impairment: Results of a pharmacokinetic study indicate that peak plasma concentrations or AUC of pitavastatin were 1.3- or 1.6-fold higher, respectively, in patients with mild (Child-Pugh class A) hepatic impairment compared with those in healthy individuals. In patients with moderate (Child-Pugh class B) hepatic impairment, peak plasma concentrations or AUC of pitavastatin were 2.7- or 3.8 fold higher, respectively, compared with those in healthy individuals.
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