Impact of Cilostazol Pharmacokinetics on the Development of Cardiovascular Side Effects in Patients with Cerebral Infarction

Yokoyama, Tasuku; Yamauchi, Shigeru; Yamagata, Keishi; Kaneshiro, Yuta; Urano, Yumiko; Murata, Keiji; Maeda, Toshio; Asahara, Yoshinori; Kagawa, Yoshiyuki

doi:10.1248/bpb.b21-00535

Cited by 3 publications

(2 citation statements)

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“…The therapeutic concentration of cilostazol (100 mg/twice daily) is in the concentration range of 2-10 µM and can vary under the fed and fasted states. 48,49 It is well established that aspirin alone or in association with the P2Y 12 blockers (clopidogrel, prasugrel, or ticagrelor) reduce the risk of acute thrombotic events. Aspirin is one of the oldest antiplatelet agents and trials in the past few decades were conducted in a manner that aspirin was always presented in the arm groups, even in the presence of more efficacious P2Y 12 blockers.…”

Section: Discussionmentioning

confidence: 99%

“…Cilostazol potentiated by, approximately, 1000‐fold (considering the therapeutic concentration of ticagrelor, that is in the range of 1–2 µM), the inhibitory response induced by ticagrelor in both groups. The therapeutic concentration of cilostazol (100 mg/twice daily) is in the concentration range of 2–10 µM and can vary under the fed and fasted states 48,49 …”

Section: Discussionmentioning

confidence: 99%

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Adenosine diphosphate‐induced aggregation is enhanced in platelets obtained from patients with thrombotic primary antiphospholipid syndrome (t‐PAPS): Role of P2Y12‐cAMP signaling pathway

Leonardi

Lescano

Costa

et al. 2022

Journal of Thrombosis and Haemostasis

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Background Thrombotic antiphospholipid syndrome (t‐PAPS) is characterized by arterial, venous, or microvascular occlusions, which are explained, in part, by the presence of antiphospholipid (aPL) antibodies. Although there is much evidence indicating that isolated aPL antibodies increase the activity of platelets obtained from healthy volunteers, platelet function in t‐PAPS has not been as widely studied. Objective To evaluate platelet reactivity in t‐PAPS patients. Methods Platelet aggregation, protein expression, and cyclic nucleotide levels were carried out in platelet rich plasma (PRP) or washed platelets (WPs) obtained from t‐PAPS or healthy volunteers. Results ADP‐induced aggregation was significantly higher in PRP obtained from t‐PAPS than obtained from the control. The protein expression of P2Y12 receptor and Gs alpha was significantly higher and lower, respectively in WPs from t‐PAPS patients. In PRP incubated with iloprost or sodium nitroprusside, the residual platelet reactivity induced by ADP was still higher in PRP from t‐PAPS than from the control. Lower intracellular levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) were observed in unstimulated PRP from t‐PAPS patients. The protein expression of soluble guanylate cyclase subunits and phosphodiesterases types 3 and 5 did not differ. The antiplatelet activity of ticagrelor was similar between the groups and cilostazol significantly potentiated this response. Isolated aPL antibodies obtained from t‐PAPS patients potentiated ADP‐induced aggregation in healthy platelets but did not affect the inhibitory responses induced by iloprost or sodium nitroprusside. Conclusions The overexpression of P2Y12 receptor, accompanied by lower levels of cAMP and cGMP levels produced greater amplitude of ADP aggregation in platelets from t‐PAPS patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%