CYP2C19 and CYP3A4 activity and ADP-induced platelet reactivity
in prasugrel- or ticagrelor-treated STEMI patients: monocentric
study in PRAGUE-18 trial participants

J 2020

CYP2C19 and CYP3A4 activity and ADP-induced platelet reactivity in prasugrel- or ticagrelor-treated STEMI patients: monocentric study in PRAGUE-18 trial participants

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 prasugrel- or ticagrelor-treated STEMI patients: monocentric study in PRAGUE-18 trial participants

Autoři

MÁCHAL, Jan (203 Česká republika, garant, domácí), Ota HLINOMAZ (203 Česká republika), Katarína KOSTOLANSKÁ (703 Slovensko, domácí), Ondřej PEŠ (203 Česká republika, domácí), Alena MÁCHALOVÁ (203 Česká republika, domácí), Zbyněk ŠPLÍCHAL (203 Česká republika, domácí), Zuzana MOŤOVSKÁ (703 Slovensko) a Jan JUŘICA (203 Česká republika, domácí)

Vydání

Xenobiotica, Abingdon, UK, Taylor & Francis Group, 2020, 0049-8254

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 1.908

Kód RIV

RIV/00216224:14110/20:00115677

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1080/00498254.2020.1731625

UT WoS

000523756800001

Klíčová slova anglicky

Cytochrome P450; prasugrel; ticagrelor; ADP test; aggregation; lansoprazole

Štítky

14110512, 14110516, 14110518, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 4. 3. 2021 12:18, Mgr. Tereza Miškechová

Anotace

V originále

We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after a loading dose of 60 mg prasugrel or 180 mg ticagrelor in patients with ST-elevation myocardial infarction (STEMI). Further, we assessed the contribution of CYP2C19 polymorphisms and medication to the CYP enzymatic activity. Patients with STEMI were randomly assigned to the treatment with prasugrel (n = 51) or ticagrelor (n = 46). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotyped for CYP2C19 *2 and *17 alleles. In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose positively correlated with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002), a marker of CYP2C19 metabolic activity, and negatively with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = -0.35, p = 0.018). CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio, but without any effect on the ADP-induced platelet reactivity. The treatment with amiodarone, a CYP3A4 inhibitor, influenced neither the metabolic ratios nor the ADP-induced platelet reactivity. The CYP3A4 and CYP2C19 metabolic activity is associated with ADP-induced platelet reactivity in prasugrel-treated, but not ticagrelor-treated patients with STEMI.

Návaznosti

MUNI/A/1132/2017, interní kód MU

Název: Behaviorální psychofarmakologie a farmakokinetika v preklinickém výzkumu léčiv

Investor: Masarykova univerzita, Behaviorální psychofarmakologie a farmakokinetika v preklinickém výzkumu léčiv, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

MUNI/A/1167/2019, interní kód MU

Název: Příspěvek (bio)chemických technik ke studiu molekulární podstaty vybraných patologických jevů a onemocnění

Investor: Masarykova univerzita, Příspěvek (bio)chemických technik ke studiu molekulární podstaty vybraných patologických jevů a onemocnění, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

Citovat

MÁCHAL, Jan, Ota HLINOMAZ, Katarína KOSTOLANSKÁ, Ondřej PEŠ, Alena MÁCHALOVÁ, Zbyněk ŠPLÍCHAL, Zuzana MOŤOVSKÁ a Jan JUŘICA. CYP2C19 and CYP3A4 activity and ADP-induced platelet reactivity in prasugrel- or ticagrelor-treated STEMI patients: monocentric study in PRAGUE-18 trial participants. Xenobiotica. Abingdon, UK: Taylor & Francis Group, 2020, roč. 50, č. 8, s. 929-938. ISSN 0049-8254. Dostupné z: https://dx.doi.org/10.1080/00498254.2020.1731625.

@article{1657320,
   author = {Máchal, Jan and Hlinomaz, Ota and Kostolanská, Katarína and Peš, Ondřej and Máchalová, Alena and Šplíchal, Zbyněk and Moťovská, Zuzana and Juřica, Jan},
   article_location = {Abingdon, UK},
   article_number = {8},
   doi = {http://dx.doi.org/10.1080/00498254.2020.1731625},
   keywords = {Cytochrome P450; prasugrel; ticagrelor; ADP test; aggregation; lansoprazole},
   language = {eng},
   issn = {0049-8254},
   journal = {Xenobiotica},
   title = {CYP2C19 and CYP3A4 activity and ADP-induced platelet reactivity in prasugrel- or ticagrelor-treated STEMI patients: monocentric study in PRAGUE-18 trial participants},
   url = {https://www.tandfonline.com/doi/abs/10.1080/00498254.2020.1731625?journalCode=ixen20},
   volume = {50},
   year = {2020}
}

TY  - JOUR
ID  - 1657320
AU  - Máchal, Jan - Hlinomaz, Ota - Kostolanská, Katarína - Peš, Ondřej - Máchalová, Alena - Šplíchal, Zbyněk - Moťovská, Zuzana - Juřica, Jan
PY  - 2020
TI  - CYP2C19 and CYP3A4 activity and ADP-induced platelet reactivity in prasugrel- or ticagrelor-treated STEMI patients: monocentric study in PRAGUE-18 trial participants
JF  - Xenobiotica
VL  - 50
IS  - 8
SP  - 929-938
EP  - 929-938
PB  - Taylor & Francis Group
SN  - 00498254
KW  - Cytochrome P450
KW  - prasugrel
KW  - ticagrelor
KW  - ADP test
KW  - aggregation
KW  - lansoprazole
UR  - https://www.tandfonline.com/doi/abs/10.1080/00498254.2020.1731625?journalCode=ixen20
L2  - https://www.tandfonline.com/doi/abs/10.1080/00498254.2020.1731625?journalCode=ixen20
N2  - We assessed the contribution of CYP2C19 and CYP3A4 metabolic activity to the ADP-induced platelet aggregation 1h and 24h after a loading dose of 60 mg prasugrel or 180 mg ticagrelor in patients with ST-elevation myocardial infarction (STEMI). Further, we assessed the contribution of CYP2C19 polymorphisms and medication to the CYP enzymatic activity. Patients with STEMI were randomly assigned to the treatment with prasugrel (n = 51) or ticagrelor (n = 46). Metabolic activity of CYP2C19 and CYP3A4 was assessed by the rate of 5-hydroxylation and sulfoxidation of lansoprazole. Further, patients were genotyped for CYP2C19 *2 and *17 alleles. In prasugrel-treated patients, high ADP-induced platelet reactivity 1h after the loading dose positively correlated with 5OH-lansoprazole/lansoprazole ratio (r = 0.44, p = 0.002), a marker of CYP2C19 metabolic activity, and negatively with lansoprazole-sulfone/lansoprazole ratio, which reflects CYP3A4 metabolic activity (r = -0.35, p = 0.018). CYP2C19 poor metabolizers had lower 5OH-lansoprazole/lansoprazole ratio and higher lansoprazole-sulfone/lansoprazole ratio, but without any effect on the ADP-induced platelet reactivity. The treatment with amiodarone, a CYP3A4 inhibitor, influenced neither the metabolic ratios nor the ADP-induced platelet reactivity. 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, Zbyněk ŠPLÍCHAL, Zuzana MOŤOVSKÁ a Jan JUŘICA. CYP2C19 and CYP3A4 activity and ADP-induced platelet reactivity in prasugrel- or ticagrelor-treated STEMI patients: monocentric study in PRAGUE-18 trial participants. \textit{Xenobiotica}. Abingdon, UK: Taylor \&{} Francis Group, 2020, roč.~50, č.~8, s.~929-938. ISSN~0049-8254. Dostupné z: https://dx.doi.org/10.1080/00498254.2020.1731625.

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