Cilostazol \u2014 How It Works
Clinical pharmacology details from the US FDA-approved label: how Cilostazol works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Cilostazol and several of its metabolites inhibit phosphodiesterase III activity and suppress cAMP degradation with a resultant increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation, respectively.
Cilostazol reversibly inhibits platelet aggregation induced by a variety of stimuli, including thrombin, ADP, collagen, arachidonic acid, epinephrine, and shear stress.
Cardiovascular effects: Cilostazol affects both vascular beds and cardiovascular function.
It produces heterogeneous dilation of vascular beds, with greater dilation in femoral beds than in vertebral, carotid or superior mesenteric arteries.
Renal arteries were not responsive to the effects of cilostazol.
In dogs or cynomolgus monkeys, cilostazol increased heart rate, myocardial contractile force, and coronary blood flow as well as ventricular automaticity, as would be expected for a PDE III inhibitor.
Left ventricular contractility was increased at doses required to inhibit platelet aggregation.
A-V conduction was accelerated.
In humans, heart rate increased in a dose-proportional manner by a mean of 5.1 and 7.4 beats per minute in patients treated with 50 and 100 mg twice daily, respectively.
12.2 Pharmacodynamics Cilostazol’s effects on platelet aggregation were evaluated in both healthy subjects and in patients with stable symptoms of cerebral thrombosis, cerebral embolism, transient ischemic attack, or cerebral arteriosclerosis over a range of doses from 50 mg every day to 100 mg three times a day.
Cilostazol significantly inhibited platelet aggregation in a dose-dependent manner.
The effects were observed as early as 3 hours post-dose and lasted up to 12 hours following a single dose.
Following chronic administration and withdrawal of cilostazol, the effects on platelet aggregation began to subside 48 hours after withdrawal and returned to baseline by 96 hours with no rebound effect.
A cilostazol dosage of 100 mg twice daily consistently inhibited platelet aggregation induced with arachidonic acid, collagen and adenosine diphosphate (ADP).
Bleeding time was not affected by cilostazol administration.
Effects on circulating plasma lipids have been examined in patients taking cilostazol.
After 12 weeks, as compared to placebo, cilostazol 100 mg twice daily produced a reduction in triglycerides of 29.3 mg/dL (15%) and an increase in HDL-cholesterol of 4.0 mg/dL (≅ 10%).
Drug Interactions Aspirin Short-term (less than or equal to 4 days) coadministration of aspirin with cilostazol increased the inhibition of ADP- induced ex vivo platelet aggregation by 22% to 37% when compared to either aspirin or cilostazol alone.
Short-term (less than or equal to 4 days) coadministration of aspirin with cilostazol increased the inhibition of arachidonic acid-induced ex vivo platelet aggregation by 20% compared to cilostazol alone and by 48% compared to aspirin alone.
However, short- term coadministration of aspirin with cilostazol had no clinically significant impact on PT, aPTT, or bleeding time compared to aspirin alone.