Cilostazol

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Cilostazol
Cilostazol.svg
Systematic (IUPAC) name
6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-
3,4-dihydro-2(1H)-quinolinone
Clinical data
Trade names Pletal
AHFS/Drugs.com monograph
MedlinePlus a601038
Pregnancy cat.
Legal status
?
Routes Oral
Pharmacokinetic data
Protein binding 95–98%
Metabolism Hepatic (CYP3A4- and CYP2C19-mediated)
Half-life 11–13 hours
Excretion Renal
Identifiers
CAS number 73963-72-1 YesY
ATC code B01AC23
PubChem CID 2754
DrugBank DB01166
ChemSpider 2652 YesY
UNII N7Z035406B YesY
KEGG D01896 YesY
ChEBI CHEBI:31401 YesY
ChEMBL CHEMBL799 YesY
Chemical data
Formula C20H27N5O2 
Mol. mass 369.46 g/mol
 YesY (what is this?)  (verify)

Cilostazol /sɨˈlɒstəzɒl/ is a quinolinone-derivative medication used in the alleviation of the symptom of intermittent claudication in individuals with peripheral vascular disease. It is manufactured by Otsuka Pharmaceutical Co. under the trade name Pletal.

Although drugs similar to cilostazol have increased the risk of death in patients with congestive heart failure, studies of significant size have not addressed people without the disease.

Cilostazol is a phosphodiesterase inhibitor with therapeutic focus on cAMP. It inhibits platelet aggregation and is a direct arterial vasodilator. Its main effects are dilation of the arteries supplying blood to the legs and decreasing platelet coagulation.

Mechanism[edit]

Cilostazol is a selective inhibitor of 3-type phosphodiesterase (PDE3) with therapeutic focus on increasing cAMP. An increase in cAMP results in an increase in the active form of PKA, which is directly related with an inhibition in platelet aggregation. PKA also prevents the activation of an enzyme (myosin light-chain kinase) that is important in the contraction of smooth muscle cells, thereby exerting its vasodilatory effect.

Clinical use[edit]

Cilostazol is approved for the treatment of intermittent claudication. The typical dose is 100 mg twice a day. The effects may take as long as 3 months to be evident and has been shown to improve pain-free walking distance by 50%.

Cilostazol is also frequently used off-label, at the same dose, for treatment of intracranial atherosclerosis and secondary stroke prevention [reference Stroke. 2005; 36: 782-786 Published online before print March 3, 2005, doi:10.1161/01.STR.0000157667.06542.b7 online http://stroke.ahajournals.org/content/36/4/782.full]

In people with heart failure[edit]

Cilostazol, clearly effective for a debilitating condition whose current treatment is often inadequate[citation needed], is a member of a pharmacologic class that is dangerous to people with severe heart failure and unstudied in other people. Cilostazol has been studied in people without heart failure, without evidence of harm, but much more data would be needed to determine that there is no risk at all. Although cilostazol would not be approvable for a trivial condition the Cardio-Renal Advisory Committee and FDA concluded that fully informed patients and physicians should be able to choose to use it to treat intermittent claudication. Patient and physician labeling will describe the basis for concern and the incomplete information available.[1]

Adverse effects[edit]

Possible side effects of cilostazol use include headache (the most common), diarrhea, abnormal stools, increased heart rate, and palpitations.[2]

Interactions[edit]

Cilostazol is metabolized by CYP3A4 and CYP2C19, two isoenzymes of the cytochrome P450 system. Drugs that inhibit CYP3A4, such as itraconazole, erythromycin, ketoconazole, and diltiazem, are known to interact with cilostazol. The proton pump inhibitor omeprazole, a potent inhibitor of CYP2C19, increases exposure to the active metabolite of cilostazol.[2]

There has been a single report of grapefruit juice possibly increasing the effects of cilostazol;[3] some drug information sources list this as a possible interaction.[4][5][6] The FDA-approved labeling of cilostazol notes that grapefruit juice (which is a CYP3A4 inhibitor) increases the drug's maximum concentration by around 50%.[2]

See also[edit]

References[edit]

  1. ^ Center for Drug Evaluation and Research (August 11, 1999). "Approval of Cilostazol". U.S. Food and Drug Administration. Retrieved 2007-04-30. 
  2. ^ a b c "Cilostazol: Official FDA information, side effects and uses.". Drugs.com. February 2008. Retrieved 2008-09-22. 
  3. ^ Taniguchi K, Ohtani H, Ikemoto T, Miki A, Hori S, Sawada Y (October 2007). "Possible case of potentiation of the antiplatelet effect of cilostazol by grapefruit juice". J Clin Pharm Ther 32 (5): 457–9. doi:10.1111/j.1365-2710.2007.00844.x. PMID 17875111. 
  4. ^ "Cilostazol for peripheral arterial disease". Yahoo! Health. Retrieved 2008-09-21. 
  5. ^ "Cilostazol". MedicineNet.com. May 25, 1999. Retrieved 2008-09-22. 
  6. ^ Cerner-Multum, Inc. (November 29, 2007). "Consumer Drug Information: Cilostazol". Drugs.com. Retrieved 2008-09-22. 

External links[edit]