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Also known as: 73963-72-1, Pletal, Cilostazole, Pletaal, Opc-13013, Cilostazolum

Molecular Formula

C₂₀H₂₇N₅O₂

Molecular Weight

369.5 g/mol

InChI Key

RRGUKTPIGVIEKM-UHFFFAOYSA-N

FDA UNII

N7Z035406B

A quinoline and tetrazole derivative that acts as a phosphodiesterase type 3 inhibitor, with anti-platelet and vasodilating activity. It is used in the treatment of PERIPHERAL VASCULAR DISEASES; ISCHEMIC HEART DISEASE; and in the prevention of stroke.

Cilostazol is a Phosphodiesterase 3 Inhibitor. The mechanism of action of cilostazol is as a Phosphodiesterase 3 Inhibitor.

1 2D Structure

Cilostazol

2 Identification

2.1 Computed Descriptors

2.1.1 IUPAC Name

6-[4-(1-cyclohexyltetrazol-5-yl)butoxy]-3,4-dihydro-1H-quinolin-2-one

2.1.2 InChI

InChI=1S/C20H27N5O2/c26-20-12-9-15-14-17(10-11-18(15)21-20)27-13-5-4-8-19-22-23-24-25(19)16-6-2-1-3-7-16/h10-11,14,16H,1-9,12-13H2,(H,21,26)

2.1.3 InChI Key

RRGUKTPIGVIEKM-UHFFFAOYSA-N

2.1.4 Canonical SMILES

C1CCC(CC1)N2C(=NN=N2)CCCCOC3=CC4=C(C=C3)NC(=O)CC4

2.2 Other Identifiers

2.2.1 UNII

N7Z035406B

2.3 Synonyms

2.3.1 MeSH Synonyms

1. 6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)-3,4-dihydro-2(1h)-quinolinone

2. Opc 13013

3. Opc-13013

4. Pletal

2.3.2 Depositor-Supplied Synonyms

1. 73963-72-1

2. Pletal

3. Cilostazole

4. Pletaal

5. Opc-13013

6. Cilostazolum

7. Opc-21

8. Cilostazolum [inn-latin]

9. Opc 13013

10. Opc 21

11. 6-[4-(1-cyclohexyltetrazol-5-yl)butoxy]-3,4-dihydro-1h-quinolin-2-one

12. 6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)-3,4-dihydro-2(1h)-quinolinone

13. 6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)-3,4-dihydroquinolin-2(1h)-one

14. Chebi:31401

15. 6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)-3,4-dihydrocarbostyril

16. 3,4-dihydro-6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)-2(1h)-quinolinone

17. Nsc-758936

18. 6-[4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy]-3,4-dihydroquinolin-2(1h)-one

19. Mls000028470

20. 6-[4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1h)-quinolinone

21. 6-[4-(1-cyclohexyl-1h-1,2,3,4-tetrazol-5-yl)butoxy]-1,2,3,4-tetrahydroquinolin-2-one

22. N7z035406b

23. Ncgc00015207-07

24. Smr000058428

25. Dsstox_cid_25132

26. Dsstox_rid_80693

27. Dsstox_gsid_45132

28. 2(1h)-quinolinone, 6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)-3,4-dihydro-

29. Cas-73963-72-1

30. Pletal (tn)

31. Sr-01000003107

32. Brn 3632107

33. Unii-n7z035406b

34. 2(1h)-quinolinone, 6-[4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy]-3,4-dihydro-

35. Cilostazol,(s)

36. Cilostazol-[d11]

37. Mfcd00866780

38. Cilostazol [usan:usp:inn:ban:jan]

39. Tocris-1692

40. Cilostazol [mi]

41. Opera_id_488

42. Cilostazol [inn]

43. Cilostazol [jan]

44. Spectrum2_001118

45. Spectrum3_001170

46. Spectrum4_000772

47. Spectrum5_001762

48. Cilostazol [usan]

49. Lopac-c-0737

50. Cilostazol [vandf]

51. Chembl799

52. 6-[4-(1-cyclohexyl-1h-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1h)-quinolinone

53. C 0737

54. Cilostazol [mart.]

55. Cilostazol [usp-rs]

56. Cilostazol [who-dd]

57. Lopac0_000218

58. Regid_for_cid_2754

59. Schembl16128

60. Bspbio_002759

61. Kbiogr_001184

62. Mls000758281

63. Mls000759507

64. Mls001076067

65. Mls002153891

66. Spectrum1505230

67. Spbio_001256

68. Cilostazol (jp17/usp/inn)

69. Gtpl7148

70. Cilostazol [orange Book]

71. Dtxsid9045132

72. Hsdb 8312

73. Kbio3_002259

74. Bcpp000279

75. Cilostazol [usp Monograph]

76. Hms1922n15

77. Hms2093m14

78. Hms2096f16

79. Hms2234c06

80. Hms3260l17

81. Hms3268o09

82. Hms3412b18

83. Hms3654j13

84. Hms3676b18

85. Hms3713f16

86. Pharmakon1600-01505230

87. Act02663

88. Bcp03724

89. Zinc1552174

90. Tox21_110098

91. Tox21_500218

92. Bdbm50225508

93. Ccg-39646

94. Nsc758936

95. S1294

96. Akos015855512

97. Cilostazol, >=98% (hplc), Powder

98. Opc 13013; Opc 21; Pletaal

99. Tox21_110098_1

100. Ac-4334

101. Am90304

102. Bcp9000530

103. Cs-1759

104. Db01166

105. Ks-5154

106. Lp00218

107. Nsc 758936

108. Sdccgsbi-0050206.p003

109. 2(1h)-quinolinone, 3,4-dihydro-6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)-

110. 2(1h)-quionlinone, 6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)-3,4-dihydro-

111. Ncgc00015207-01

112. Ncgc00015207-02

113. Ncgc00015207-03

114. Ncgc00015207-04

115. Ncgc00015207-05

116. Ncgc00015207-06

117. Ncgc00015207-08

118. Ncgc00015207-09

119. Ncgc00015207-10

120. Ncgc00015207-11

121. Ncgc00015207-12

122. Ncgc00015207-25

123. Ncgc00022153-02

124. Ncgc00022153-04

125. Ncgc00022153-05

126. Ncgc00022153-06

127. Ncgc00022153-07

128. Ncgc00260903-01

129. Hy-17464

130. Bcp0726000145

131. Retal;pletal;opc 21;pletaal;cilostal

132. Sbi-0050206.p002

133. Eu-0100218

134. Ft-0602474

135. Ft-0645036

136. Ft-0665038

137. Sw199053-2

138. D01896

139. F20538

140. Ab00382988-14

141. Ab00382988_15

142. Ab00382988_16

143. 963c721

144. A837982

145. Q258591

146. Q-200854

147. Sr-01000003107-2

148. Sr-01000003107-4

149. Sr-01000003107-7

150. Brd-k67017579-001-04-2

151. Brd-k67017579-001-05-9

152. Brd-k67017579-001-07-5

153. Brd-k67017579-001-13-3

154. Brd-k67017579-001-17-4

155. Sr-01000003107-10

156. Cilastatin Sodium, Antibiotic For Culture Media Use Only

157. Cilostazol, United States Pharmacopeia (usp) Reference Standard

158. 6-[4-(1-cyclohexyl-1,2,3,4-tetrazol-5-yl)butoxy]-3,4-dihydrocarbostyril

159. 6-[4-(l-cyclohexyl-1,2,3,4-tetrazol-5-yl)butoxyl]-3,4-dihydrocarbostyril

160. Cilostazol, Pharmaceutical Secondary Standard; Certified Reference Material

161. 6-(4-(1-cyclohexyl-1h-tetrazol-5-yl)butoxy)quinoline-2,3(1h,4h)-dione

162. 6-[4-(1-cyclohexyl-1h-tetrazol-5-yl)-butoxy]-3,4-dihydro-1h-quinolin-2-one

163. 89332-50-3

2.4 Create Date

2005-03-25

3 Chemical and Physical Properties

Molecular Formula	C₂₀H₂₇N₅O₂
Molecular Weight	369.5 g/mol
XLogP3	3.1
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	7
Exact Mass	369.21647512 g/mol
Monoisotopic Mass	369.21647512 g/mol
Topological Polar Surface Area	81.9 Å²
Heavy Atom Count	27
Formal Charge	0
Complexity	485
Isotope Atom Count	0
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Covalently Bonded Unit Count	1

4 Drug and Medication Information

4.1 Drug Information

1 of 4
Drug Name	Cilostazol
PubMed Health	Cilostazol (By mouth)
Drug Classes	Platelet Aggregation Inhibitor
Drug Label	Cilostazol is a quinolinone derivative that inhibits cellular phosphodiesterase (more specific for phosphodiesterase III). The empirical formula of cilostazol is C20H27N5O2, and its molecular weight is 369.46. Cilostazol is 6-[4-(1-cyclohexyl-1H-tetr...
Active Ingredient	Cilostazol
Dosage Form	Tablet
Route	oral; Oral
Strength	100mg; 50mg
Market Status	Prescription
Company	Mylan Pharms; Actavis Elizabeth; Breckenridge Pharm; Teva; Apotex; Pliva Hrvatska Doo; Biokey; Sandoz; Mylan; Roxane

2 of 4
Drug Name	Pletal
PubMed Health	Cilostazol (By mouth)
Drug Classes	Platelet Aggregation Inhibitor
Drug Label	PLETAL (cilostazol) is a quinolinone derivative that inhibits cellular phosphodiesterase (more specific for phosphodiesterase III). The empirical formula of cilostazol is C20H27N5O2, and its molecular weight is 369.46. Cilostazol is 6-[4-(1-cyclohexy...
Active Ingredient	Cilostazol
Dosage Form	Tablet
Route	Oral
Strength	100mg; 50mg
Market Status	Prescription
Company	Otsuka

3 of 4
Drug Name	Cilostazol
PubMed Health	Cilostazol (By mouth)
Drug Classes	Platelet Aggregation Inhibitor
Drug Label	Cilostazol is a quinolinone derivative that inhibits cellular phosphodiesterase (more specific for phosphodiesterase III). The empirical formula of cilostazol is C20H27N5O2, and its molecular weight is 369.46. Cilostazol is 6-[4-(1-cyclohexyl-1H-tetr...
Active Ingredient	Cilostazol
Dosage Form	Tablet
Route	oral; Oral
Strength	100mg; 50mg
Market Status	Prescription
Company	Mylan Pharms; Actavis Elizabeth; Breckenridge Pharm; Teva; Apotex; Pliva Hrvatska Doo; Biokey; Sandoz; Mylan; Roxane

4 of 4
Drug Name	Pletal
PubMed Health	Cilostazol (By mouth)
Drug Classes	Platelet Aggregation Inhibitor
Drug Label	PLETAL (cilostazol) is a quinolinone derivative that inhibits cellular phosphodiesterase (more specific for phosphodiesterase III). The empirical formula of cilostazol is C20H27N5O2, and its molecular weight is 369.46. Cilostazol is 6-[4-(1-cyclohexy...
Active Ingredient	Cilostazol
Dosage Form	Tablet
Route	Oral
Strength	100mg; 50mg
Market Status	Prescription
Company	Otsuka

4.2 Therapeutic Uses

/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Cilostazol is included in the database.

NIH/NLM; ClinicalTrials.Gov. Available from, as of March 17, 2016: https://clinicaltrials.gov/ct2/results?term=cilostazol&Search=Search

Pletal is indicated for the reduction of symptoms of intermittent claudication, as demonstrated by an increased walking distance. /Included in US product label/

NIH; DailyMed. Current Medication Information for Pletal (Cilostazol) Tablet (Updated: July 2015). Available from, as of January 20, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=24d75b58-bafb-4440-b8d7-4f4079c08b0b

Because of its antiplatelet activity, cilostazol has been used alone or in combination with other antiplatelet agents (e.g., aspirin, clopidogrel) to prevent thrombosis and restenosis following coronary angioplasty/stent implantation. /NOT included in US product label/

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 1528

Cilostazol has been used for the secondary prevention of stroke in patients with a history of noncardioembolic stroke or transient ischemic attacks (TIAs). /NOT included in US product label/

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 1528

/EXPL THER/ We conducted a randomized, double blind, placebo controlled trial to assess the efficacy and safety of cilostazol, a selective inhibitor of phosphodiesterase 3, in patients with vasospastic angina (VSA). Cilostazol has been shown to induce vascular dilatation, but its efficacy in patients with VSA is unknown. Between October 2011 and July 2012, 50 patients with confirmed VSA who had >/= 1 angina episodes/week despite amlodipine therapy (5 mg/day) were randomly assigned to receive either cilostazol (up to 200 mg/day) or placebo for 4 weeks. All patients were given diaries to record the frequency and severity of chest pain (0-10 grading). The primary endpoint was the relative reduction of the weekly incidence of chest pain. Baseline characteristics were similar between the two groups. Among 49 evaluable patients (25 in the cilostazol group, 24 in the placebo group), the primary endpoint was significantly greater in the cilostazol group compared with the placebo group (-66.5 +/- 88.6% vs -17.6 +/- 140.1%, respectively, p=0.009). The secondary endpoints, including a change in the frequency of chest pain (-3.7 +/- 0.5 vs -1.9 +/- 0.6, respectively, p=0.029), a change in the chest pain severity scale (-2.8 +/- 0.4 vs -1.1 +/- 0.4, respectively, p=0.003), and the proportion of chest pain-free patients (76.0% vs 33.3%, respectively, p=0.003) also significantly favoured cilostazol. Headache was the most common adverse event in both groups (40.0% vs 20.8%, respectively, p=0.217). Cilostazol is an effective therapy for patients with VSA uncontrolled by conventional amlodipine therapy, and has no serious side effects.

PMID:24934484 Shin ES et al; Heart 100 (19): 1531-6 (2014)

4.3 Drug Warning

/BOXED WARNING/ WARNING: CONTRAINDICATED IN HEART FAILURE PATIENTS. Pletal is contraindicated in patients with heart failure of any severity. Cilostazol and several of its metabolites are inhibitors of phosphodiesterase III. Several drugs with this pharmacologic effect have caused decreased survival compared to placebo in patients with class III-IV heart failure.

Rare cases of thrombocytopenia or leukopenia progressing to agranulocytosis have been reported when cilostazol was not immediately discontinued; agranulocytosis was reversible with discontinuance of cilostazol.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 1529

Information is limited regarding the safety and efficacy of concurrent use of cilostazol and clopidogrel. Currently it is unknown whether concurrent therapy with cilostazol and clopidogrel has additive effects on bleeding time. Caution should be used and bleeding times monitored during such concurrent therapy.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 1529

Cilostazol may induce tachycardia, palpitation, tachyarrhythmia or hypotension. The increase in heart rate associated with cilostazol is approximately 5 to 7 bpm. Patients with a history of ischemic heart disease may be at risk for exacerbations of angina pectoris or myocardial infarction.

For more Drug Warnings (Complete) data for Cilostazol (10 total), please visit the HSDB record page.

4.4 Drug Indication

Indicated for the alleviation of symptoms of intermittent claudication (pain in the legs that occurs with walking and disappears with rest).

5 Pharmacology and Biochemistry

5.1 Pharmacology

Cilostazol reduces the symptoms of intermittent claudication, as indicated by an increased walking distance. Intermittent claudication is pain in the legs that occurs with walking and disappears with rest. The pain occurs due to reduced blood flow to the legs.

5.2 MeSH Pharmacological Classification

Fibrinolytic Agents

Fibrinolysin or agents that convert plasminogen to FIBRINOLYSIN. (See all compounds classified as Fibrinolytic Agents.)

Neuroprotective Agents

Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. (See all compounds classified as Neuroprotective Agents.)

Vasodilator Agents

Drugs used to cause dilation of the blood vessels. (See all compounds classified as Vasodilator Agents.)

Bronchodilator Agents

Agents that cause an increase in the expansion of a bronchus or bronchial tubes. (See all compounds classified as Bronchodilator Agents.)

Platelet Aggregation Inhibitors

Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. (See all compounds classified as Platelet Aggregation Inhibitors.)

Phosphodiesterase 3 Inhibitors

Compounds that specifically inhibit PHOSPHODIESTERASE 3. (See all compounds classified as Phosphodiesterase 3 Inhibitors.)

5.3 FDA Pharmacological Classification

5.3.1 Active Moiety

CILOSTAZOL

5.3.2 FDA UNII

N7Z035406B

5.3.3 Pharmacological Classes

Phosphodiesterase 3 Inhibitors [MoA]; Phosphodiesterase 3 Inhibitor [EPC]

5.4 ATC Code

B - Blood and blood forming organs

B01 - Antithrombotic agents

B01A - Antithrombotic agents

B01AC - Platelet aggregation inhibitors excl. heparin

B01AC23 - Cilostazol

5.5 Absorption, Distribution and Excretion

Absorption

Cilostazol is absorbed after oral administration. A high fat meal increases absorption, with an approximately 90% increase in C_max and a 25% increase in AUC. Absolute bioavailability is not known.

Route of Elimination

Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Cilostazol is eliminated predominately by metabolism and subsequent urinary excretion of metabolites. The primary route of elimination was via the urine (74%), with the remainder excreted in feces (20%). No measurable amount of unchanged cilostazol was excreted in the urine, and less than 2% of the dose was excreted as 3,4-dehydro-cilostazol. About 30% of the dose was excreted in urine as 4'-trans-hydroxy-cilostazol.

/MILK/ Transfer of cilostazol into milk has been reported in rats.

Following oral administration of a single 100-mg dose of cilostazol with a high-fat meal, peak plasma cilostazol concentrations and area under the plasma concentration-time curve (AUC) increased by approximately 90 and 25%, respectively.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 1529

Pletal is absorbed after oral administration. A high fat meal increases absorption, with an approximately 90% increase in Cmax and a 25% increase in AUC. Absolute bioavailability is not known.

NIH; DailyMed. Current Medication Information for Pletal (Cilostazol) Tablet (Updated: July 2015). Available from, as of January 25, 2016: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=24d75b58-bafb-4440-b8d7-4f4079c08b0b

The primary route of elimination was via the urine (74%), with the remainder excreted in feces (20%). No measurable amount of unchanged cilostazol was excreted in the urine, and less than 2% of the dose was excreted as 3,4-dehydro-cilostazol. About 30% of the dose was excreted in urine as 4'-trans-hydroxy-cilostazol. The remainder was excreted as other metabolites, none of which exceeded 5%. There was no evidence of induction of /microsomal enzymes/.

For more Absorption, Distribution and Excretion (Complete) data for Cilostazol (7 total), please visit the HSDB record page.

5.6 Metabolism/Metabolites

Hepatic. Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Two metabolites are active, with one metabolite appearing to account for at least 50% of the pharmacologic (PDE III inhibition) activity after administration of cilostazol.

Following oral administration of 100 mg radiolabeled cilostazol, 56% of the total analytes in plasma was cilostazol, 15% was 3,4-dehydro-cilostazol (4-7 times as active as cilostazol), and 4% was 4'-trans-hydroxy-cilostazol (20% as active as cilostazol).

Cilostazol is eliminated predominantly by metabolism and subsequent urinary excretion of metabolites. Based on in vitro studies, the primary isoenzymes involved in cilostazol's metabolism are CYP3A4 and, to a lesser extent, CYP2C19. The enzyme responsible for metabolism of 3,4-dehydro-cilostazol, the most active of the metabolites, is unknown.

Cilostazol is extensively metabolized by hepatic cytochrome P-450 enzymes, mainly 3A4, and, to a lesser extent, 2C19, with metabolites largely excreted in urine. Two metabolites are active, with one metabolite appearing to account for at least 50% of the pharmacologic (PDE III inhibition) activity after administration of Pletal.

The pharmacokinetics of cilostazol was investigated after oral and intravenous administration in both male and female rats. After oral administration, area under serum concentration-time curve (AUC) was about 35-fold higher in female rats than in male rats, and absolute bioavailability was about 5.8-fold higher in female rats than in male rats. Total body clearance (CL(total)) for female rats was around one-sixth of that for male rats. In vivo hepatic clearance (CL(h)) calculated based on isolated liver perfusion studies was even higher than or around 90% of the in vivo CL(total) of cilostazol for female and male rats, respectively, indicating that cilostazol is mainly eliminated by the liver in both male and female rats. In vitro metabolism studies utilizing hepatic microsomes and recombinant cytochrome (CYP) isoforms clearly indicated that major metabolites of cilostazol were generated extensively with hepatic microsomes of male rats and that male-predominant CYP3A2 and male-specific CYP2C11 were mainly responsible for the hepatic metabolism of cilostazol. Therefore, the great sex differences in the pharmacokinetics of cilostazol were mainly attributed to the large difference in hepatic metabolism. Our experimental results also suggested that the substantial metabolism of cilostazol in the small intestine and its possible saturation would be responsible for dose-dependent bioavailability in both male and female rats.

PMID:21718207 Kamada N et al; Xenobiotica 41 (10): 903-13 (2011)

Cilostazol has known human metabolites that include OPC-13217 and OPC-13326.

S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

5.7 Biological Half-Life

11-13 hours.

Cilostazol and its active metabolites have apparent elimination half-lives of about 11-13 hours.

5.8 Mechanism of Action

Cilostazol and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation.

Cilostazol, a phosphodiesterase 3, has been widely used in patients with arterial disease and is known to have additional beneficial effects on dyslipidemia. However, the effect of cilostazol on hepatic steatosis has not been fully elucidated. We investigated the effect of cilostazol on hepatic ABCA1 expression and hepatic steatosis in diet-induced obesity mice model. Hepatic ABCA1 expression and lipid accumulation were analyzed in HepG2 cell lines treated with cilostazol. Male C57BL/6 mice were randomly divided into three groups: (1) fed normal chow diet with vehicle; (2) fed high-fat diet (HFD) with vehicle; (3) fed HFD with cilostazol. Cilostazol (30 mg/kg) was orally administered once daily for 9 weeks. Cilostazol significantly enhanced ABCA1 expression and restored ABCA1 expression reduced by palmitate in HepG2 cells. Cilostazol treatment ameliorated lipid accumulation induced by palmitate, and this effect was diminished when ABCA1 or LRP1 was silenced by small interference RNA. After silencing of LRP1, ABCA1 expression was decreased in HepG2 cells. Cilostazol significantly enhanced hepatic ABCA1 expression and decreased hepatic fat in HFD-fed mice. Hepatic expression of cleaved caspase-3 and PARP1 was also decreased in HFD-fed mice treated with cilostazol. Cilostazol ameliorated hepatic steatosis and increased ABCA1 expression in the hepatocytes. Enhancing ABCA1 expression with cilostazol represents a potential therapeutic avenue for treatment of hepatic steatosis.

PMID:26362727 Jeon BH et al; Metabolism 64 (11): 1444-53 (2015)

Cilostazol, a quinolinone-derivative selective phosphodiesterase (PDE) inhibitor, is a platelet-aggregation inhibitor and arterial vasodilator. Although the mechanism of action of cilostazol has not been fully elucidated, the drug appears to inhibit activation of cellular PDE type III (PDE III), resulting in suppressed degradation, and thus increased concentrations, of cyclic adenosine-3',5'-monophosphate (cAMP) in platelets and blood vessels. Increased cAMP concentrations are thought to result in arterial vasodilation and inhibition of platelet aggregation.

American Society of Health-System Pharmacists 2015; Drug Information 2015. Bethesda, MD. 2015, p. 1529

API SUPPLIERS

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LGM Pharma

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03

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04

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05

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06

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07

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08

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Cohance Lifesciences is a leading CDMO and API platform, offering products and services across all phases of a molecule’s lifecycle from development to commercialzation. With our expertise in complex chemistries, we provide end-to-end CDMO services to global innovators and have delivered numerous projects from concept to commercialization over the years.As a global API player, we serve customers across nearly 60 countries with 80+ molecules backed by robust R&D, regulatory capabilities and manufacturing infrastructure. We are among the top backward integrated exporters of pellets and have strong development and manufacturing capabilities.

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Jai Radhe Sales was founded in 1999 as an out-of-the-box distribution firm specializing in the global supply of high-quality pharmaceutical ingredients. The firm provides complete sourcing solutions for pharmaceutical products from India, including technical and regulatory assistance. It believes in providing its customers with high-quality products at reasonable prices. It has always endeavored to achieve global standards in the field of pharmaceuticals and has carved out a niche for itself through new methods based on current market needs. Today, it has established itself as a truly global company, with exports to almost every continent.

05

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Founded in 1935, TAPI Technology & API Services has a long-standing tradition of advancing health through innovation and dedication. Today, we proudly build upon this legacy, driving progress in the pharmaceutical industry. Leveraging our extensive experience and world-class expertise, we deliver one of the most comprehensive API portfolios in the industry. Additionally, we provide tailored CDMO services, harnessing our proficiency in diverse technologies to meet our partners' unique needs, ensuring flexibility and excellence in every project.

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06

Allastir

India

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07

Amsal Chem Private Ltd.

India

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Amsal Chem Private Ltd.

India

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About the Company : Amsal Chem Private Limited' GMP and ISO certified, globally largest manufacturer-exporter of ISONIAZID having over 50 % world market share, registered with various MOH: alongwith P...

Amsal Chem Private Limited' GMP and ISO certified, globally largest manufacturer-exporter of ISONIAZID having over 50 % world market share, registered with various MOH: alongwith PYRAZINAMIDE, NICOTINIC ACID[NIACIN] and NICOTINAMIDE(NIACINAMIDE) complying to BP/EP/USP specifications.Other API's: Amlodipine Besilate, Cilostazol, Desloratadine and Glimepiride.Nutraceuticals: Alpha Picolinic acid, Di-Picolinic acid, Chromium Picolinate, Chromium Polynicotinate and Zinc Picolinate.Intermediates: 2Mercapto 5Methoxy Benzimidazole, Isonicotinic acid, Isonicotinamide, Methyl Isonicotinate(Isonicotinic acid Methyl Ester) and Methyl Nicotinate (Nicotinic acid Methyl Ester).Having manufacturing capacity of 1,200 MT's annually on idea mix basis.DMF's available.

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Formil Quimica Ltd

Brazil

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09

Medilux Laboratories

India

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Nifty Labs

India

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API Reference Price

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CO LTD,","supplierCountry":"CHINA","foreign_port":"SHANGHAI","customer":"IPCA LABORATORIES","customerCountry":"INDIA","quantity":"1840.00","actualQuantity":"1840","unit":"KGS","unitRateFc":"92","totalValueFC":"171059.6","currency":"USD","unitRateINR":"7737.6","date":"07-Oct-2023","totalValueINR":"14237170.2","totalValueInUsd":"171059.6","indian_port":"JNPT","hs_no":"29339990","bill_no":"8186431","productDescription":"API","marketType":"REGULATED MARKET","country":"CHINA","selfForZScoreResived":"Pharma Grade","supplierPort":"SHANGHAI","supplierAddress":"ROOM 2109-1-2,XIHU INTERNATIONAL SCIENCE AND TECHNOLOGY BUILDING NO.391 WENER ROA D,XIHU DISTRICT,HANGZHO China","customerAddress":"48, KANDIVLI INDUSTRIAL ESTATE,"},{"dataSource":"API Import","activeIngredients":"","year":"2024","qtr":"Q3","strtotime":1722450600,"product":"CILOSTAZOL RELATED COMPOUND B (QTY: 1 X 50MG, VALUE USD: 838) (FOC)","address":"P.NO. D6 D8, SY.NO. 234\/2,234\/3,","city":"TURKAPALLY(V),SHAMEERPET, HYDERABAD","supplier":"USP","supplierCountry":"INDIA","foreign_port":"WASHINGTON, DULLES I","customer":"UNITED STATES PHARMACOPEIA - INDIA PRIVATE LIMITED","customerCountry":"INDIA","quantity":"0.00","actualQuantity":"0.00005","unit":"KGS","unitRateFc":"16760000","totalValueFC":"854.2","currency":"USD","unitRateINR":"1433000000","date":"01-Aug-2024","totalValueINR":"71650","totalValueInUsd":"854.2","indian_port":"Hyderabad Air","hs_no":"29337990","bill_no":"4827338","productDescription":"Re-Import","marketType":"REGULATED MARKET","country":"INDIA","selfForZScoreResived":"Pharma Grade","supplierPort":"WASHINGTON, DULLES I","supplierAddress":"7135 ENGLISH MUFFIN WAY FREDERICK,MD 21704 USA Frederick, , United States United States","customerAddress":"P.NO. D6 D8, SY.NO. 234\/2,234\/3,"}]

Number of Transactions

Total Quantity (KGS)

Total Value (USD)

Quantity (KGS) & Unit rate (USD/KGS) over time

API Imports and Exports

Importing Country	Total Quantity (KGS)	Average Price (USD/KGS)	Number of Transactions

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DOSAGE - TABLET;ORAL - 100MG **Federal Regist...DOSAGE - TABLET;ORAL - 100MG **Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons**

USFDA APPLICATION NUMBER - 20863

DOSAGE - TABLET;ORAL - 50MG **Federal Registe...DOSAGE - TABLET;ORAL - 50MG **Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons**

USFDA APPLICATION NUMBER - 20863

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ACTIVE PHARMA INGREDIENTS

39 API Suppliers

12 USDMF

14 JDMF

5 EU WC

26 KDMF

6 NDC API

20 Listed Suppliers

$ API Reference Price

DEVELOPMENTS

1 Drugs in Development

INTERMEDIATES

11 Intermediates Suppliers

FINISHED DOSAGE FORMULATIONS

71 FDF Dossiers

28 FDA Orange Book

29 Europe

14 Listed Dossiers

DRUG PRODUCT COMPOSITIONS

TABLET;ORAL - 100MG **Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons**

TABLET;ORAL - 50MG **Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons**

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EXCIPIENTS BY APPLICATIONS

72 Fillers, Diluents & Binders

42 Coating Systems & Additives

41 Disintegrants & Superdisintegrants

39 Direct Compression

27 Granulation

25 Controlled & Modified Release

18 Co-Processed Excipients

17 Thickeners and Stabilizers

17 Lubricants & Glidants

10 Solubilizers

9 Taste Masking

9 Chewable & Orodispersible Aids

6 Film Formers & Plasticizers

5 API Stability Enhancers

5 Empty Capsules

4 Vegetarian Capsules

4 Emulsifying Agents

3 Rheology Modifiers

TABLET;ORAL - 100MG Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons

TABLET;ORAL - 50MG Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons