CYP2C19 and CYP3A4 Activity and ADP-induced Platelet Reactivity
in Patients with STEMI Treated by Prasugrel or Ticagrelor

k 2018

CYP2C19 and CYP3A4 Activity and ADP-induced Platelet Reactivity in Patients with STEMI Treated by Prasugrel or Ticagrelor

MÁCHAL, Jan, Ota HLINOMAZ, Katarína KOSTOLANSKÁ, Ondřej PEŠ, Alena MÁCHALOVÁ et. al.

Základní údaje

Originální název

CYP2C19 and CYP3A4 Activity and ADP-induced Platelet Reactivity in Patients with STEMI Treated by Prasugrel or Ticagrelor

Autoři

MÁCHAL, Jan, Ota HLINOMAZ, Katarína KOSTOLANSKÁ, Ondřej PEŠ, Alena MÁCHALOVÁ a Jan JUŘICA

Vydání

86th European Atherosclerosis Society Congress, 2018

Další údaje

Typ výsledku

Prezentace na konferencích

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

DOI

http://dx.doi.org/10.1016/j.atherosclerosis.2018.06.246

UT WoS

000442512600260

Klíčová slova česky

prasugrel; ticagrelor; cytochrom P450; agregace krevních destiček

Klíčová slova anglicky

prasugrel; ticagrelor; cytochrome P450; platelet aggregation

Příznaky

Mezinárodní význam

Změněno: 27. 9. 2018 12:31, MUDr. Jan Máchal, Ph.D.

Anotace

V originále

Aim: We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after the loading dose of 60 mg prasugrel or 180 mg ticagrelor in the patients with ST-elevations myocardial infarction (STEMI) treated by percutaneous coronary intervention. Further, we assessed the contribution of CYP2C19 polymorphisms and amiodarone treatment to the CYP 450 enzymatic activity. Methods: Total number of 89 patients with STEMI were randomly assigned to the treatment with prasugrel (n = 46) or ticagrelor (n = 43). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotypized for CYP2C19 *2 and *17 alleles and the data about concomitant treatment were collected, where amiodarone was considered as CYP3A4 inhibitor. Results: In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose negatively correlated with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = -0.35, p = 0.018) and positively with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002). There was no significant effect with respect to CYP2C19 or CYP3A4 metabolic activity after 24h or in the ticagrelor group. CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio compared to the intermediate and extensive metabolizers, but this was not reflected in the ADP-induced platelet reactivity. The treatment with amiodarone did not influence neither the metabolic ratios nor the ADP-induced platelet reactivity. Conclusions: The CYP3A4 and CYP2C19 metabolic activity is associated with ADP-induced platelet reactivity in prasugrel-treated, but not ticagrelor-treated patients with STEMI.

Citovat

MÁCHAL, Jan, Ota HLINOMAZ, Katarína KOSTOLANSKÁ, Ondřej PEŠ, Alena MÁCHALOVÁ a Jan JUŘICA. CYP2C19 and CYP3A4 Activity and ADP-induced Platelet Reactivity in Patients with STEMI Treated by Prasugrel or Ticagrelor. In 86th European Atherosclerosis Society Congress. 2018. Dostupné z: https://dx.doi.org/10.1016/j.atherosclerosis.2018.06.246.

@proceedings{1416608,
   author = {Máchal, Jan and Hlinomaz, Ota and Kostolanská, Katarína and Peš, Ondřej and Máchalová, Alena and Juřica, Jan},
   booktitle = {86th European Atherosclerosis Society Congress},
   doi = {http://dx.doi.org/10.1016/j.atherosclerosis.2018.06.246},
   keywords = {prasugrel; ticagrelor; cytochrome P450; platelet aggregation},
   title = {CYP2C19 and CYP3A4 Activity and ADP-induced Platelet Reactivity in Patients with STEMI Treated by Prasugrel or Ticagrelor},
   url = {http://services.aimgroup.eu/ASPClient/prgsci/main.asp?SessionID=3065997&IDSes=},
   year = {2018}
}

TY  - CONF
ID  - 1416608
AU  - Máchal, Jan - Hlinomaz, Ota - Kostolanská, Katarína - Peš, Ondřej - Máchalová, Alena - Juřica, Jan
PY  - 2018
TI  - CYP2C19 and CYP3A4 Activity and ADP-induced Platelet Reactivity in Patients with STEMI Treated by Prasugrel or Ticagrelor
KW  - prasugrel
KW  - ticagrelor
KW  - cytochrome P450
KW  - platelet aggregation
UR  - http://services.aimgroup.eu/ASPClient/prgsci/main.asp?SessionID=3065997&IDSes=
L2  - http://services.aimgroup.eu/ASPClient/prgsci/main.asp?SessionID=3065997&IDSes=
N2  - Aim: We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after the loading dose of 60 mg prasugrel or 180 mg ticagrelor in the patients with ST-elevations myocardial infarction (STEMI) treated by percutaneous coronary intervention. Further, we assessed the contribution of CYP2C19 polymorphisms and amiodarone treatment to the CYP 450 enzymatic activity. Methods: Total number of 89 patients with STEMI were randomly assigned to the treatment with prasugrel (n = 46) or ticagrelor (n = 43). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotypized for CYP2C19 *2 and *17 alleles and the data about concomitant treatment were collected, where amiodarone was considered as CYP3A4 inhibitor. Results: In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose negatively correlated with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = -0.35, p = 0.018) and positively with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002). There was no significant effect with respect to CYP2C19 or CYP3A4 metabolic activity after 24h or in the ticagrelor group. CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio compared to the intermediate and extensive metabolizers, but this was not reflected in the ADP-induced platelet reactivity. The treatment with amiodarone did not influence neither the metabolic ratios nor the ADP-induced platelet reactivity. Conclusions: The CYP3A4 and CYP2C19 metabolic activity is associated with ADP-induced platelet reactivity in prasugrel-treated, but not ticagrelor-treated patients with STEMI.
ER  -

MÁCHAL, Jan, Ota HLINOMAZ, Katarína KOSTOLANSKÁ, Ondřej PEŠ, Alena MÁCHALOVÁ a Jan JUŘICA. CYP2C19 and CYP3A4 Activity and ADP-induced Platelet Reactivity in Patients with STEMI Treated by Prasugrel or Ticagrelor. In \textit{86th European Atherosclerosis Society Congress}. 2018. Dostupné z: https://dx.doi.org/10.1016/j.atherosclerosis.2018.06.246.

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