Impaired bioavailability and antiplatelet effect of high-dose
clopidogrel in patients after cardiopulmonary resuscitation
(CPR)

J 2013

Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)

SOUČKOVÁ, L.; R. OPATŘILOVÁ; Pavel SUK; I. Jr ČUNDRLE; M. PAVLIK et al.

Základní údaje

Originální název

Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)

Autoři

SOUČKOVÁ, L.; R. OPATŘILOVÁ; Pavel SUK ; I. Jr ČUNDRLE; M. PAVLIK; V. ZVONÍČEK; Ota HLINOMAZ a Vladimír ŠRÁMEK

Vydání

EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, HEIDELBERG, SPRINGER HEIDELBERG, 2013, 0031-6970

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 2.697

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/13:00071680

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1007/s00228-012-1360-0

UT WoS

000317335200002

Klíčová slova anglicky

Clopidogrel; Pharmacokinetics; Thrombelastography; HPLC

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 31. 1. 2014 16:51, Soňa Böhmová

Anotace

V originále

Purpose Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. Methods In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. Results The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5-1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50%) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p=0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r=0.79; p<0.001). Conclusion The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.

Citovat

SOUČKOVÁ, L.; R. OPATŘILOVÁ; Pavel SUK; I. Jr ČUNDRLE; M. PAVLIK; V. ZVONÍČEK; Ota HLINOMAZ a Vladimír ŠRÁMEK. Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR). EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY. HEIDELBERG: SPRINGER HEIDELBERG, 2013, roč. 69, č. 3, s. 309-317. ISSN 0031-6970. Dostupné z: https://doi.org/10.1007/s00228-012-1360-0.

@article{1162114,
   author = {Součková, L. and Opatřilová, R. and Suk, Pavel and Čundrle, I. Jr and Pavlik, M. and Zvoníček, V. and Hlinomaz, Ota and Šrámek, Vladimír},
   article_location = {HEIDELBERG},
   article_number = {3},
   doi = {https://doi.org/10.1007/s00228-012-1360-0},
   keywords = {Clopidogrel; Pharmacokinetics; Thrombelastography; HPLC},
   language = {eng},
   issn = {0031-6970},
   journal = {EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY},
   title = {Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)},
   volume = {69},
   year = {2013}
}

TY  - JOUR
ID  - 1162114
AU  - Součková, L. - Opatřilová, R. - Suk, Pavel - Čundrle, I. Jr - Pavlik, M. - Zvoníček, V. - Hlinomaz, Ota - Šrámek, Vladimír
PY  - 2013
TI  - Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR)
JF  - EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
VL  - 69
IS  - 3
SP  - 309-317
EP  - 309-317
PB  - SPRINGER HEIDELBERG
SN  - 00316970
KW  - Clopidogrel
KW  - Pharmacokinetics
KW  - Thrombelastography
KW  - HPLC
N2  - Purpose Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. Methods In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. Results The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5-1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50%) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p=0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r=0.79; p<0.001). Conclusion The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.
ER  -

SOUČKOVÁ, L.; R. OPATŘILOVÁ; Pavel SUK; I. Jr ČUNDRLE; M. PAVLIK; V. ZVONÍČEK; Ota HLINOMAZ a Vladimír ŠRÁMEK. Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR). \textit{EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY}. HEIDELBERG: SPRINGER HEIDELBERG, 2013, roč.~69, č.~3, s.~309-317. ISSN~0031-6970. Dostupné z: https://doi.org/10.1007/s00228-012-1360-0.

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