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.

Basic information

Original name

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

Authors

MÁCHAL, Jan (203 Czech Republic, guarantor, belonging to the institution), Ota HLINOMAZ (203 Czech Republic), Katarína KOSTOLANSKÁ (703 Slovakia, belonging to the institution), Ondřej PEŠ (203 Czech Republic, belonging to the institution), Alena MÁCHALOVÁ (203 Czech Republic, belonging to the institution), Zbyněk ŠPLÍCHAL (203 Czech Republic, belonging to the institution), Zuzana MOŤOVSKÁ (703 Slovakia) and Jan JUŘICA (203 Czech Republic, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 1.908

RIV identification code

RIV/00216224:14110/20:00115677

Organization unit

Faculty of Medicine

DOI

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

UT WoS

000523756800001

Keywords in English

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

Abstract

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.

Links

MUNI/A/1132/2017, interní kód MU

Name: Behaviorální psychofarmakologie a farmakokinetika v preklinickém výzkumu léčiv

Investor: Masaryk University, Category A

MUNI/A/1167/2019, interní kód MU

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

Investor: Masaryk University, Category A

Citovat

MÁCHAL, Jan, Ota HLINOMAZ, Katarína KOSTOLANSKÁ, Ondřej PEŠ, Alena MÁCHALOVÁ, Zbyněk ŠPLÍCHAL, Zuzana MOŤOVSKÁ and 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, vol. 50, No 8, p. 929-938. ISSN 0049-8254. Available from: 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 and 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, vol.~50, No~8, p.~929-938. ISSN~0049-8254. Available from: https://dx.doi.org/10.1080/00498254.2020.1731625.

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