Abstract
Objective: Clopidogrel is activated by cytochrome P450 3A (CYP3A) to generate an active metabolite that inhibits adenosine diphosphate (ADP)-induced platelet aggregation through irreversible binding to the platelet P2Y12 receptor. The objective of this study was to assess the effect of the CYP3A5 genotype on the pharmacokinetics and antiplatelet effect of clopidogrel in healthy subjects. Methods: Twenty-two healthy subjects (CYP3A5*1/*1, n=6; CYP3A5*1/*3, n=8; CYP3A5*3/*3, n=8) were recruited. After the administration of a loading dose of 300 mg of clopidogrel followed by 75 mg once daily for 6 days, plasma concentrations of clopidogrel and SR26334, an inactive metabolite, were measured for 24 h. The antiplatelet effect of clopidogrel was also measured, by determining the inhibition of ADP-induced platelet aggregation for 168 h, according to CYP3A5 genotype. Results: Mean plasma concentration profiles of clopidogrel and SR26334 were comparable between CYP3A5 genotype groups. In addition, the CYP3A5 genotype did not affect the pharmacokinetics of either clopidogrel or SR26334. CYP3A5 genotype also did not modulate the inhibitory effect of clopidogrel on platelet aggregation. Conclusion: The CYP3A5*3 genotype plays a minor role in causing interindividual variability of the disposition of clopidogrel and its antiplatelet effect in humans.
| Original language | English |
|---|---|
| Pages (from-to) | 589-597 |
| Number of pages | 9 |
| Journal | European Journal of Clinical Pharmacology |
| Volume | 64 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2008 Jun 1 |
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Keywords
- Clopidogrel
- CYP3A5*3
- Cytochrome P450 (CYP3A5)
- Platelet aggregation
- SR26334
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
Cite this
Effect of CYP3A5*3 genotype on the pharmacokinetics and antiplatelet effect of clopidogrel in healthy subjects. / Kim, Kyoung Ah; Park, Pil Whan; Park, Ji-Young.
In: European Journal of Clinical Pharmacology, Vol. 64, No. 6, 01.06.2008, p. 589-597.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Effect of CYP3A5*3 genotype on the pharmacokinetics and antiplatelet effect of clopidogrel in healthy subjects
AU - Kim, Kyoung Ah
AU - Park, Pil Whan
AU - Park, Ji-Young
PY - 2008/6/1
Y1 - 2008/6/1
N2 - Objective: Clopidogrel is activated by cytochrome P450 3A (CYP3A) to generate an active metabolite that inhibits adenosine diphosphate (ADP)-induced platelet aggregation through irreversible binding to the platelet P2Y12 receptor. The objective of this study was to assess the effect of the CYP3A5 genotype on the pharmacokinetics and antiplatelet effect of clopidogrel in healthy subjects. Methods: Twenty-two healthy subjects (CYP3A5*1/*1, n=6; CYP3A5*1/*3, n=8; CYP3A5*3/*3, n=8) were recruited. After the administration of a loading dose of 300 mg of clopidogrel followed by 75 mg once daily for 6 days, plasma concentrations of clopidogrel and SR26334, an inactive metabolite, were measured for 24 h. The antiplatelet effect of clopidogrel was also measured, by determining the inhibition of ADP-induced platelet aggregation for 168 h, according to CYP3A5 genotype. Results: Mean plasma concentration profiles of clopidogrel and SR26334 were comparable between CYP3A5 genotype groups. In addition, the CYP3A5 genotype did not affect the pharmacokinetics of either clopidogrel or SR26334. CYP3A5 genotype also did not modulate the inhibitory effect of clopidogrel on platelet aggregation. Conclusion: The CYP3A5*3 genotype plays a minor role in causing interindividual variability of the disposition of clopidogrel and its antiplatelet effect in humans.
AB - Objective: Clopidogrel is activated by cytochrome P450 3A (CYP3A) to generate an active metabolite that inhibits adenosine diphosphate (ADP)-induced platelet aggregation through irreversible binding to the platelet P2Y12 receptor. The objective of this study was to assess the effect of the CYP3A5 genotype on the pharmacokinetics and antiplatelet effect of clopidogrel in healthy subjects. Methods: Twenty-two healthy subjects (CYP3A5*1/*1, n=6; CYP3A5*1/*3, n=8; CYP3A5*3/*3, n=8) were recruited. After the administration of a loading dose of 300 mg of clopidogrel followed by 75 mg once daily for 6 days, plasma concentrations of clopidogrel and SR26334, an inactive metabolite, were measured for 24 h. The antiplatelet effect of clopidogrel was also measured, by determining the inhibition of ADP-induced platelet aggregation for 168 h, according to CYP3A5 genotype. Results: Mean plasma concentration profiles of clopidogrel and SR26334 were comparable between CYP3A5 genotype groups. In addition, the CYP3A5 genotype did not affect the pharmacokinetics of either clopidogrel or SR26334. CYP3A5 genotype also did not modulate the inhibitory effect of clopidogrel on platelet aggregation. Conclusion: The CYP3A5*3 genotype plays a minor role in causing interindividual variability of the disposition of clopidogrel and its antiplatelet effect in humans.
KW - Clopidogrel
KW - CYP3A53
KW - Cytochrome P450 (CYP3A5)
KW - Platelet aggregation
KW - SR26334
UR - http://www.scopus.com/inward/record.url?scp=42549112187&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42549112187&partnerID=8YFLogxK
U2 - 10.1007/s00228-008-0471-0
DO - 10.1007/s00228-008-0471-0
M3 - Article
C2 - 18385991
AN - SCOPUS:42549112187
VL - 64
SP - 589
EP - 597
JO - European Journal of Clinical Pharmacology
JF - European Journal of Clinical Pharmacology
SN - 0031-6970
IS - 6
ER -