mRNA expression of drug metabolism enzymes and transporter genes at birth using human umbilical cord blood |
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| Authors: | Virginia Neyro Valéry Elie Yves Médard Evelyne Jacqz‐Aigrain |
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| Affiliation: | 1. Department of Pediatric Clinical Pharmacology and Pharmacogenetics, Assistance Publique – H?pitaux de Paris, H?pital Robert Debré, Paris, France;2. Ecole Doctorale MTCI – Paris Descartes University, Paris, France;3. APHP INSERM Clinical Investigation Center CIC1426, H?pital Robert Debré, Paris, France;4. Paris Diderot University, Sorbonne Paris‐Cité, Paris, France |
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| Abstract: | Growth and maturation changes are mainly responsible for differences in drug pharmacokinetics and pharmacodynamics observed between adults and children, especially neonates. Ontogeny of drug‐metabolizing enzymes and transporters plays an important role in drugs interindividual pharmacokinetic variability but data are limited in both term and preterm neonates. This study aimed to characterize mRNA expression of the main drug‐metabolizing enzymes and transport proteins involved in drug disposition, using umbilical cord blood (UCB), according to gender, gestational age, and genetic background. A large panel of genes was quantified as follows: cytochrome P450 system (n = 12), UGT family (n = 6), TPMT and transporters (n = 3), in 56 samples of UCB of twin neonates. Gene expression was measured using real‐time reverse transcription polymerase chain reaction with 18S rRNA as the endogenous control for normalization of data. Relative expression of the samples was expressed using the 2?ΔΔCt method for comparison of gene expression levels. Twenty genes were expressed in UCB at birth with variable levels of expression and tissue‐specific gene expression when compared to data on the fetal liver. Gestational age, gender, and genetic background influenced the expression of the genes tested. Easily accessible UCB samples will enable further studies to evaluate the influence of covariates. This suggests that these covariates need to be considered when assessing substrate drugs disposition mediated by these metabolizing enzymes and transporters in the neonatal population. |
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| Keywords: | ABC transporters drug metabolism enzymes gene expression
mRNA
ontogeny |
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