pitavastatin; nisvastatin; itavastatin (Livalo)

Introduction

FDA approved 2009, release expected 2010

Indications

• treatment of hypercholestolemia

Pharmacokinetics

• maximum plasma levels 1/1/5 hours after oral dose
• bioavailability 43-51%
• protein binding 99%
• only slightly lipophilic
• metabolized by CYP2C9 & to a lesser extent CYP2C8
• not a prodrug; no active metabolites
• 1/2 life of 12 hours
• renal excretion 15%

Adverse effects

• constipation
• myalgia
• arthralgia
• back pain

• drug adverse effects of HMG CoA reductase inhibitors
• drug adverse effects of anti-hyperlipidemic agents

Drug interactions

• avoid use of pitavastatin in combination with cyclosporine, tacrolimus, everolimus, sirolimus
• close monitoring for myalgia with coadministration of colchicine
• acceptable for use with gemfibrozil

• drug interaction(s) anticonvulsants with statins
• drug interaction(s) of statins with vitamin D
• drug interaction(s) of statins with SSRIs
• drug interaction(s) of statins with influenza virus vaccines
• drug interaction(s) of statins with macrolide
• drug interaction(s) of statins with antiviral protease inhibitors
• drug interaction(s) of statins with fibrates

Mechanism of action

• inhibition of HMG CoA reductase
• drug's base structure has a unique cyclopropyl group, which may lead to greater LDL cholesterol clearance & plasma cholesterol reduction compared with other statins

More general terms

• lipophilic statin

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5282451
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6366718
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5282452
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=11251522