Pitavastatin

Synonyms :
Pitavastatia, Pitavastatine, Pitavastatinum

Status : approved

Category

Hypolipidemic Agents

Therapeutic Classification

LIPID MODIFYING AGENTS, PLAIN

CARDIOVASCULAR SYSTEM
LIPID MODIFYING AGENTS
LIPID MODIFYING AGENTS, PLAIN

Description

Pitavastatin a lipid-lowering agent that belongs to the statin class of medications for treatment of dyslipidemia. It is also used for primary and secondary prevention of cardiovascular disease. FDA approved in Aug 3, 2009.

Used

Pitavastatin is used to lower serum levels of total cholesterol, LDL-C, apolipoprotein B, and triglycerides, and raise levels of HDL-C for the treatment of dyslipidemia.

Mechanism Of Action

Pitavastatin is lipid-lowering agent that works to control the synthesis of cholesterol via competitive inhibition of the liver enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. As a result, a compensatory increase in LDL-receptor expression can be observed which facilitates an increase LDL catabolism.

Dosage

Form Route Strength
Tablet, film coated oral 1 mg
Tablet, film coated oral 1.045 mg
Tablet, film coated oral 2 mg
Tablet, film coated oral 2.09 mg
Tablet, film coated oral 4 mg
Tablet, film coated oral 4.18 mg

Pharmacodynamics

The magnitude of LDL-C reduction by pitavastatin (2 mg and 4 mg) is comparable to atorvastatin (10 mg and 20 mg) and simvastatin (20 mg and 40 mg). It also does not prolong the QTc interval to a clinically significant degree.

Toxic Effect

The most frequent adverse reactions (rate ≥2.0% in at least one marketed dose) were myalgia, back pain, diarrhea, constipation and pain in extremity.

Metabolism

Pitavastatin is mainly metabolized by liver. It undergoes glucuronidation by uridine 5-diphosphate glucuronosyl transferases (UGT1A3 and UGT2B7) to form the major circulating metabolite, pitavastatin lactone. The cytochrome P450 system has little involvement with the metabolism of pitavastatin. There is some metabolism by CYP2C9 and to a lesser extent, CYP2C8. Studies suggest that concomitant therapy with drugs that are involved with the cytochrome P450 system will not effect the pharmacokinetics of pitavastatin.

Absorption

Bioavailability = 51%; Time to peak, plasma = 1 hour; Pitavastatin was absorbed in the small intestine but very little in the colon. Cmax decreases by 43% if pitavastatin is taken with a fatty meal but there are no significant changes to AUC or baseline LDL levels compared to fasting state. The Cmax and AUC of pitavastatin did not differ following evening or morning drug administration.

Half Life

Plasma elimination half-lfie = 12 hours

Protein Binding

>99% protein bound in human plasma, mainly to albumin and alpha 1-acid glycoprotein.

Elimination Route

79% in feces and 15% excreted in urine.

Clearance

CL/F (apparent clearance), 4 mg, healthy male Korean subjects = 23.6 L/h

Volume of Distribution

148 L

Chemical Classification

This compound belongs to the class of organic compounds known as phenylquinolines. These are heterocyclic compounds containing a quinoline moiety substituted with a phenyl group.

Phenylquinolines

Organic compounds

Organoheterocyclic compounds

Quinolines and derivatives

Phenylquinolines

Salt : Pitavastatin Calcium

Chemical Name

Pitavastatia

Brands

name Dosage form Country
Livalo tablet, film coated US
Livalo tablet, film coated US
Livalo tablet, film coated US
Livalo tablet, film coated US
Livalo tablet, film coated US
Livalo tablet, film coated US

Drug Drug Interactions

  •  Acipimox  : May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors.
  •  Aluminum hydroxide  : May decrease the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Atazanavir  : May increase the serum concentration of Pitavastatin.
  •  Bezafibrate  : May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin
  •  Boceprevir  : May increase the serum concentration of Pitavastatin.
  •  Bosentan  : May increase the metabolism of HMG-CoA Reductase Inhibitors.
  •  Calcium carbonate  : May decrease the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Ciprofibrate  : May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors.
  •  Clarithromycin  : May increase the serum concentration of Pitavastatin.
  •  Colchicine  : May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Cyclosporine  : Cyclosporine (Systemic) may increase the serum concentration of Pitavastatin.
  •  Daclatasvir  : May increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Danazol  : May increase the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Daptomycin  : HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of Daptomycin. Specifically, the risk of skeletal muscle toxicity may be increased.
  •  Eltrombopag  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Erythromycin  : Erythromycin (Systemic) may increase the serum concentration of Pitavastatin.
  •  Gemfibrozil  : May enhance the myopathic (rhabdomyolysis) effect of Pitavastatin. Gemfibrozil may increase the serum concentration of Pitavastatin.
  •  Magnesium oxide  : May decrease the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Niacin  : May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors.
  •  Pazopanib  : HMG-CoA Reductase Inhibitors may enhance the hepatotoxic effect of Pazopanib. Specifically, the risk for increased serum transaminase concentrations may be increased.
  •  Raltegravir  : May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors.
  •  Rifabutin  : Rifamycin Derivatives may increase the serum concentration of Pitavastatin.
  •  Rifampicin  : Rifamycin Derivatives may increase the serum concentration of Pitavastatin.
  •  Rifapentine  : Rifamycin Derivatives may increase the serum concentration of Pitavastatin.
  •  Simeprevir  : May increase the serum concentration of Pitavastatin.
  •  Sulfisoxazole  : Erythromycin (Systemic) may increase the serum concentration of Pitavastatin.
  •  Telaprevir  : May increase the serum concentration of Pitavastatin.
  •  Telithromycin  : May increase the serum concentration of Pitavastatin.
  •  Teriflunomide  : May increase the serum concentration of OATP1B1/SLCO1B1 Substrates.
  •  Trabectedin  : HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin.

Food Interactions

  • Avoid taking pitavastatin with red yeast rice. May increase risk of myopathy of pitavastatin via pharmacodynamic synergism. Red yeast rice contain monocolin K (similar to lovastatin), Take with or without food

Calculated Property

kind Value Source
logP 3.75 ALOGPS
logS -5 ALOGPS
Water Solubility 3.94e-03 g/l ALOGPS
logP 2.92 ChemAxon
IUPAC Name (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid ChemAxon
Traditional IUPAC Name pitavastatin ChemAxon
Molecular Weight 421.4608 ChemAxon
Monoisotopic Weight 421.168936466 ChemAxon
SMILES O[C@H](C[C@H](O)C=CC1=C(N=C2C=CC=CC2=C1C1=CC=C(F)C=C1)C1CC1)CC(O)=O ChemAxon
Molecular Formula C25H24FNO4 ChemAxon
InChI InChI=1S/C25H24FNO4/c26-17-9-7-15(8-10-17)24-20-3-1-2-4-22(20)27-25(16-5-6-16)21(24)12-11-18(28)13-19(29)14-23(30)31/h1-4,7-12,16,18-19,28-29H,5-6,13-14H2,(H,30,31)/b12-11+/t18-,19-/m1/s1 ChemAxon
InChIKey InChIKey=VGYFMXBACGZSIL-MCBHFWOFSA-N ChemAxon
Polar Surface Area (PSA) 90.65 ChemAxon
Refractivity 115.74 ChemAxon
Polarizability 43.76 ChemAxon
Rotatable Bond Count 8 ChemAxon
H Bond Acceptor Count 5 ChemAxon
H Bond Donor Count 3 ChemAxon
pKa (strongest acidic) 4.13 ChemAxon
pKa (strongest basic) 4.86 ChemAxon
Physiological Charge -1 ChemAxon
Number of Rings 4 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 1 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • 3-hydroxy-3-methylglutaryl-coenzyme A reductase : in Human