Pitavastatin

Last updated

Pitavastatin
Pitavastatin.svg
Clinical data
Trade names Livalo, Livazo, others
AHFS/Drugs.com Monograph
MedlinePlus a610018
License data
Pregnancy
category
  • AU:D
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • UK: POM (Prescription only)
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 60%
Protein binding 96%
Metabolism Liver (CYP2C9, minimally)
Elimination half-life 11 hours
Excretion Faeces
Identifiers
  • (3R,5S,6E)-7-[2-Cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.171.153 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C25H24FNO4
Molar mass 421.468 g·mol−1
3D model (JSmol)
  • O=C(O)C[C@H](O)C[C@H](O)/C=C/c1c(c3ccccc3nc1C2CC2)c4ccc(F)cc4
  • 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 Yes check.svgY
  • Key:VGYFMXBACGZSIL-MCBHFWOFSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering medication class of statins. [1]

Contents

Pitavastatin is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis.

It was patented in 1987 and approved for medical use in 2003. [2] It is available in Japan, South Korea and in India. [3] In the US, it received FDA approval in 2009. [4] Kowa Pharmaceuticals, a subsidiary of Kowa Company, is the owner of the American patent to pitavastatin.

Medical uses

Pitavastatin is indicated for hypercholesterolaemia (elevated cholesterol) and for the prevention of cardiovascular disease.[ citation needed ]

A 2009 study of the 104-week LIVES trial found pitavastatin increased HDL cholesterol, especially in patients with HDL lower than 40 mg/dL, who had a 24.6% rise, in addition to reducing LDL cholesterol 31.3%. [5] HDL improved in patients who switched from other statins and rose over time. In the 70-month CIRCLE observational study, pitavastatin increased HDL more than atorvastatin. [6]

It has neutral or possibly beneficial effects on glucose control. [7] As a consequence, pitavastatin is likely to be appropriate for patients with metabolic syndrome plus high LDL, low HDL and diabetes mellitus.[ citation needed ]

Side effects

Common statin-related side effects (headaches, stomach upset, abnormal liver function tests and muscle cramps) were similar to other statins. [8] Pitavastatin is a lipophilic statin. [9] [10] Reports indicate that this statin may lead to fewer muscle side effects than other statins. [11] One study found that coenzyme Q10 was not reduced as much as with certain other statins (though this is unlikely given the inherent chemistry of the HMG-CoA reductase pathway that all statin drugs inhibit). [12] [13]

There is evidence that pitavastatin does not increase insulin resistance in humans, with insulin resistance assessed by the homeostatic model assessment (HOMA-IR) method. [14]

Hyperuricemia or increased levels of serum uric acid have been reported with pitavastatin. [15]

Metabolism and interactions

Statins are metabolised in part by one or more liver cytochrome P450 enzymes, leading to an increased potential for drug interactions and problems with certain foods (such as grapefruit juice). The primary metabolism pathway of pitavastatin is glucuronidation. It is minimally metabolized by the CYP450 enzymes CYP2C9 and CYP2C8, [16] but not by CYP3A4 (which is a common source of interactions in other statins). As a result, it is less likely to interact with drugs that are metabolized via CYP3A4, which might be important for elderly patients who need to take multiple medicines. [12]

History

Pitavastatin (previously known as itavastatin, itabavastin, nisvastatin, NK-104, or NKS-104) was discovered in Japan by Nissan Chemical Industries and developed further by Kowa Pharmaceuticals, Tokyo. [12] Pitavastatin was approved for use in the United States by the FDA in August 2009, under the brand name Livalo. Pitavastatin has been also approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in UK in August 2010. Zypitamag (pitavastatin magnesium), a pharmaceutical alternative to Livalo, was approved for use in the United States by the FDA in 2017.[ citation needed ]

Society and culture

Brand names

Pitavastatin is marketed in the United States under the brand names Livalo and Zypitamag, and in the European Union and Russia under the brand name Livazo.[ citation needed ]

Research

Synthetic lethality has been demonstrated in mice with triple-negative breast cancer by combining pitavastatin with the AKT inhibitor AZD5363 (capivasertib). [17]

References

  1. ↑ Kajinami K, Takekoshi N, Saito Y (2003). "Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoA reductase inhibitor". Cardiovascular Drug Reviews. 21 (3): 199–215. doi:10.1111/j.1527-3466.2003.tb00116.x. PMID   12931254.
  2. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 473. ISBN   978-3-527-60749-5.
  3. ↑ "Zydus Cadila launches pitavastatin in India". Archived from the original on 26 September 2017. Retrieved 28 May 2006.
  4. ↑ "Pitavastatin (Livalo)--the seventh statin". The Medical Letter on Drugs and Therapeutics. 52 (1343): 57–58. July 2010. PMID   20651638.
  5. ↑ Teramoto T, Shimano H, Yokote K, Urashima M (October 2009). "Effects of pitavastatin (LIVALO Tablet) on high density lipoprotein cholesterol (HDL-C) in hypercholesterolemia". Journal of Atherosclerosis and Thrombosis. 16 (5): 654–661. doi: 10.5551/jat.1719 . PMID   19907105.
  6. ↑ Masana L (30 May 2013). "Pitavastatin in cardiometabolic disease: therapeutic profile". Cardiovascular Diabetology. 12 Suppl 1 (Suppl 1): S2. doi: 10.1186/1475-2840-12-S1-S2 . PMC   3668168 . PMID   23819752.
  7. ↑ Arsh H, Ali A, Khenhrani RR, Simran F, Dino U, Tamang S, et al. (November 2023). "Efficacy and Safety of Pitavastatin in Patients with Impaired Glucose Tolerance: An Updated Review". Current Problems in Cardiology. 48 (11) 101981. Elsevier BV. doi:10.1016/j.cpcardiol.2023.101981. PMID   37473935.
  8. ↑ Duggan ST (March 2012). "Pitavastatin: a review of its use in the management of hypercholesterolaemia or mixed dyslipidaemia". Drugs. 72 (4): 565–584. doi:10.2165/11207180-000000000-00000. PMID   22356292. S2CID   195680129.
  9. ↑ Sahebkar A, Kiaie N, Gorabi AM, Mannarino MR, Bianconi V, Jamialahmadi T, et al. (November 2021). "A comprehensive review on the lipid and pleiotropic effects of pitavastatin". Progress in Lipid Research. 84 101127. doi:10.1016/j.plipres.2021.101127. PMID   34509516. S2CID   237494271.
  10. ↑ Climent E, Benaiges D, Pedro-Botet J (20 May 2021). "Hydrophilic or Lipophilic Statins?". Frontiers in Cardiovascular Medicine. 8 687585. doi: 10.3389/fcvm.2021.687585 . PMC   8172607 . PMID   34095267.
  11. ↑ "Alternative Cholesterol-Lowering Drug for Patients Who Can't Tolerate Statins". ScienceDaily. 11 May 2013.
  12. 1 2 3 Mukhtar RY, Reid J, Reckless JP (February 2005). "Pitavastatin". International Journal of Clinical Practice. 59 (2): 239–252. doi:10.1111/j.1742-1241.2005.00461.x. PMID   15854203. S2CID   221814440.
  13. ↑ Kawashiri MA, Nohara A, Tada H, Mori M, Tsuchida M, Katsuda S, et al. (May 2008). "Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study". Clinical Pharmacology and Therapeutics. 83 (5): 731–739. doi:10.1038/sj.clpt.6100396. PMID   17957184. S2CID   20956339.
  14. ↑ Nakagomi A, Shibui T, Kohashi K, Kosugi M, Kusama Y, Atarashi H, et al. (2015). "Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia". Journal of Atherosclerosis and Thrombosis. 22 (11): 1158–1171. doi: 10.5551/jat.29520 . PMID   26084792.
  15. ↑ Ogata N, Fujimori S, Oka Y, Kaneko K (June 2010). "Effects of three strong statins (atorvastatin, pitavastatin, and rosuvastatin) on serum uric acid levels in dyslipidemic patients". Nucleosides, Nucleotides & Nucleic Acids. 29 (4–6): 321–324. doi:10.1080/15257771003741323. PMID   20544514. S2CID   30650248.
  16. ↑ "Livalo". Drugs.com ..
  17. ↑ Hillis AL, Martin TD, Manchester HE, Högström J, Zhang N, Lecky E, et al. (October 2024). "Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer". Cancer Research. 84 (19): 3250–3266. doi:10.1158/0008-5472.can-24-0970. ISSN   0008-5472.
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