What question did this study set out to answer?

To identify the cytochrome P450 enzymes responsible for dextromethorphan metabolism and characterize their developmental ontogeny in adult and fetal tissues.

February 19, 2019Developmental Pharmacology and Therapeutics

Cytochrome P450-DependentMetabolism ofDextromethorphan:Fetal and Adult Studies

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Authors

ÉJÉvelyne Jacqz-AigrainHôpital Saint-Louis TCThierry CresteilUniversité Paris-Sud

Discussion

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Implication

In vitro and in vivo analysis reveals distinct developmental timing of CYP2D6 and CYP3A in human fetuses and adults, indicating differential fetal drug clearance pathways.

Key Points

To identify the cytochrome P450 enzymes responsible for dextromethorphan metabolism and characterize their developmental ontogeny in adult and fetal tissues.
Conducted in vivo and in vitro metabolic evaluations in adult volunteers stratified by extensive and poor metabolizer phenotypes.
Assayed CYP2D6 and CYP3A gene expression, protein presence, and catalytic activity in human fetal liver microsomes starting at 17 weeks of gestation.
Performed comparative immunoinhibition studies between adult and fetal CYP3A subfamily isoforms.
CYP2D6 mediates the primary O-demethylation pathway yielding dextrorphan in adult extensive metabolizers but lacks functional activity in poor metabolizers.
CYP2D6 protein and enzymatic activity are undetectable in human fetal microsomes before birth despite significant levels of CYP2D6 RNA.
CYP3A enzymes catalyze N-demethylation to 3-methoxymorphinan and demonstrate robust catalytic activity in fetal liver tissue from the 17th week of gestation.

Cite This Study

Jacqz-Aigrain et al. (2019) studied this question.

synapsesocial.com/papers/6a735bd56cf7a6ca1f6c2f92 https://doi.org/10.1159/000480616

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Implication

In vitro and in vivo analysis reveals distinct developmental timing of CYP2D6 and CYP3A in human fetuses and adults, indicating differential fetal drug clearance pathways.

Cytochrome P450-DependentMetabolism ofDextromethorphan:Fetal and Adult Studies

Discussion

Member takes

Implication

Key Points

Cite This Study

Cytochrome P450-DependentMetabolism ofDextromethorphan:Fetal and Adult Studies

Discussion

Member takes

Implication

Key Points

Cite This Study

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