Effect of CYP2C9 Polymorphisms on the Pharmacokinetics of Indomethacin During Pregnancy.
Journal
European journal of drug metabolism and pharmacokinetics
ISSN: 2107-0180
Titre abrégé: Eur J Drug Metab Pharmacokinet
Pays: France
ID NLM: 7608491
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
pubmed:
31
8
2018
medline:
31
5
2019
entrez:
31
8
2018
Statut:
ppublish
Résumé
Cytochrome P450 (CYP) 2C9 catalyzes the biotransformation of indomethacin to its inactive metabolite O-desmethylindomethacin (DMI). The aim of this work was to determine the effect of CYP2C9 polymorphisms on indomethacin metabolism in pregnant women. Plasma concentrations of indomethacin and DMI at steady state were analyzed with a validated LC-MS/MS method. DNA was isolated from subject blood and buccal smear samples. Subjects were grouped by genotype for comparisons of pharmacokinetic parameters. For subjects with the *1/*2 genotype, the mean steady-state apparent oral clearance (CL/F Although our results are limited by sample size and are not statistically significant, these data suggest that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic ratio and an increase in the clearance of indomethacin. More data are needed to assess the impact of CYP2C9 genotype on the effectiveness of indomethacin as a tocolytic agent.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
Cytochrome P450 (CYP) 2C9 catalyzes the biotransformation of indomethacin to its inactive metabolite O-desmethylindomethacin (DMI). The aim of this work was to determine the effect of CYP2C9 polymorphisms on indomethacin metabolism in pregnant women.
METHODS
METHODS
Plasma concentrations of indomethacin and DMI at steady state were analyzed with a validated LC-MS/MS method. DNA was isolated from subject blood and buccal smear samples. Subjects were grouped by genotype for comparisons of pharmacokinetic parameters.
RESULTS
RESULTS
For subjects with the *1/*2 genotype, the mean steady-state apparent oral clearance (CL/F
CONCLUSION
CONCLUSIONS
Although our results are limited by sample size and are not statistically significant, these data suggest that certain genetic polymorphisms of CYP2C9 may lead to an increased metabolic ratio and an increase in the clearance of indomethacin. More data are needed to assess the impact of CYP2C9 genotype on the effectiveness of indomethacin as a tocolytic agent.
Identifiants
pubmed: 30159654
doi: 10.1007/s13318-018-0505-7
pii: 10.1007/s13318-018-0505-7
pmc: PMC6380929
mid: NIHMS1505389
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
CYP2C9 protein, human
EC 1.14.13.-
Cytochrome P-450 CYP2C9
EC 1.14.13.-
Indomethacin
XXE1CET956
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
83-89Subventions
Organisme : NICHD NIH HHS
ID : R01 HD083003
Pays : United States
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : U10HD04789108
Organisme : Eunice Kennedy Shriver National Institute of Child Health and Human Development
ID : R01HD083003
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