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June 6, 2026British Journal of Clinical Pharmacology

Impaired clopidogrel activation due to CYP2C19 phenoconversion after mild acute ischaemic stroke

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Key result

Mild acute ischemic stroke linked to lower clopidogrel active metabolite Cmax versus healthy controls.

  • P<0.05
  • n=33

Why the study?

Inflammatory states like acute ischaemic stroke may cause CYP2C19 phenoconversion, temporarily reducing enzyme activity and impairing clopidogrel activation.

Does mild acute ischaemic stroke reduce CYP2C19 activity and clopidogrel activation compared to healthy controls?

Comparison

Acute phase vs post-acute phase (21 days after acute ischaemic stroke)

Design

Pharmacokinetic study

Follow-up

21 days

Authors

MAMaryam AlaeiMashhad University of Medical SciencesHHHooshyar HonarmandTehran University of Medical SciencesMGMohammadreza GheiniSina Hospital

Discussion

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Overview

May reduce clopidogrel activation in mild stroke regardless of genotype; leaves open whether phenoconversion warrants adjusted monitoring or dosing.

Key Points

  • This study aims to assess the impact of phenoconversion on clopidogrel activation in mild acute ischaemic stroke patients.
  • Pharmacokinetic study conducted in Iranian patients with mild acute ischaemic stroke (NIHSS ≤ 5) prescribed clopidogrel for 21 days.
  • Genotyping performed using real-time PCR; CYP2C19 activity assessed by omeprazole metabolic ratio and maximum plasma concentration of H4‐clopi.
  • Data on laboratory parameters and demographic characteristics were recorded.
  • CYP2C19 activity significantly reduced in the acute phase, with partial recovery noted in the post-acute phase.
  • H4‐clopi Cmax was significantly lower in stroke patients compared to healthy controls in both phases (p < 0.05).
  • Inflammatory markers and NIHSS scores decreased significantly in the post-acute phase (p < 0.05).

Study Design

Type

Observational (n=33)

Structured PICO

Does mild acute ischaemic stroke reduce CYP2C19 activity and clopidogrel activation compared to healthy controls?

P
Population
33 Iranian patients (mean age 63, 34% female) with mild acute ischaemic stroke (NIHSS ≤ 5) prescribed clopidogrel, evaluated over 21 days.
E
Exposure
Clopidogrel prescribed for 21 days
C
Comparator
Healthy controls
O
Outcome
CYP2C19 activity (omeprazole metabolic ratio) and Clopidogrel metabolism (maximum plasma concentration of H4-clopi) in acute and post-acute phases (21 days)surrogate

Main Result

p-value: p=<0.05

Acute ischaemic stroke induces CYP2C19 phenoconversion, reducing clopidogrel activation regardless of genotype, suggesting genotyping alone may be insufficient to identify poor metabolizers.

Cite This Study

Alaei et al. (2026) conducted an observational in Mild acute ischaemic stroke (n=33). Mild acute ischaemic stroke vs. Healthy controls was evaluated on H4-clopi maximum plasma concentration (Cmax) (p=<0.05). Mild acute ischaemic stroke was associated with significantly lower clopidogrel active metabolite Cmax compared to healthy controls in both acute and post-acute phases (p < 0.05).

synapsesocial.com/papers/6a23b9ac71a5da9775e7583fhttps://doi.org/10.1002/bcp.70635
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Also Consider

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