What question did this study set out to answer?

This research aims to understand how ketoconazole affects the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel.

March 14, 2007Clinical Pharmacology & Therapeutics

Cytochrome P450 3A Inhibition by Ketoconazole Affects Prasugrel and Clopidogrel Pharmacokinetics and Pharmacodynamics Differently

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Why the study?

Does CYP3A inhibition by ketoconazole affect the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects?

Population

Healthy subjects

Comparison

Prasugrel or clopidogrel with ketoconazole vs Prasugrel or clopidogrel without ketoconazole

Design

RCT, randomized crossover

Follow-up

5 days per period (with 2-week washout)

Authors

NFNazar FaridOllscoil na Gaillimhe – University of Galway CPChristopher D. PayneEli Lilly (United States)DSD. S. SmallUniversity of Kentucky

Discussion

Member takes

Implication

CYP3A inhibitors may attenuate clopidogrel efficacy; confirms prasugrel activation independent of CYP3A.

Key Points

This research aims to understand how ketoconazole affects the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel.
Randomized crossover study design was used with healthy subjects.
Participants received loading and maintenance doses of prasugrel or clopidogrel, with or without ketoconazole.
A 2-week washout period was implemented between treatment periods.
Ketoconazole decreased clopidogrel's active metabolite Cmax by 34-61%.
Clopidogrel's AUC0-24 decreased by 22% (LD) to 29% (MD) after ketoconazole administration.
Prasugrel's active metabolite formation and its inhibition of platelet aggregation were unaffected by ketoconazole.

Structured PICO

Does CYP3A inhibition by ketoconazole affect the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects?

Population

Healthy subjects

Intervention

Prasugrel (60 mg loading dose, 15 mg daily maintenance for 5 days) or clopidogrel (300 mg loading dose, 75 mg daily maintenance for 5 days) with ketoconazole (400 mg/day)

Comparator

Prasugrel or clopidogrel without ketoconazole

Outcome

Active metabolite Cmax, AUC0-24, and inhibition of platelet aggregation (IPA)surrogate

CYP3A inhibition by ketoconazole significantly reduces the active metabolite formation and antiplatelet effect of clopidogrel, but not prasugrel.

Cite This Study

Farid et al. (2007) studied this question.

synapsesocial.com/papers/69fa89c79fa336b96d47d7d4 https://doi.org/10.1038/sj.clpt.6100139

Topics

Dual antiplatelet therapy

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Cytochrome P450 3A Inhibition by Ketoconazole Affects Prasugrel and Clopidogrel Pharmacokinetics and Pharmacodynamics Differently

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Cytochrome P450 3A Inhibition by Ketoconazole Affects Prasugrel and Clopidogrel Pharmacokinetics and Pharmacodynamics Differently

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

Also Consider