Clinical and genetic influencing factors on clozapine pharmacokinetics in Tunisian schizophrenic patients.
Journal
The pharmacogenomics journal
ISSN: 1473-1150
Titre abrégé: Pharmacogenomics J
Pays: United States
ID NLM: 101083949
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
18
07
2020
accepted:
22
02
2021
revised:
04
02
2021
pubmed:
19
3
2021
medline:
11
3
2022
entrez:
18
3
2021
Statut:
ppublish
Résumé
Clozapine (Clz) is an atypical antipsychotic, which its pharmacokinetics can be influenced by several factors. The CYP1A2 and CYP2C19, major enzymes implicated in Clz metabolism, present an interethnic variation on their activity caused by single nucleotide polymorphisms (SNPs). The present study investigated the influence of genetic and nongenetic factors on Clz pharmacokinetics in a southern Mediterranean population. We included adult Tunisian schizophrenic patients having received Clz and undergone a therapeutic drug monitoring (TDM) of Clz by morning C0 monitoring. The genomic DNA was extracted using a salting-out procedure. CYP1A2*1F (rs762551;-163C>A), CYP1A2*1C (rs2069514;-3860 G>A) and CYP 2C19*2 (rs4244285; 681G>A) was analyzed using PCR-RFLP. Fifty-one patients were enrolled in the study. The mutant allele (CYP1A2*1F) was the most frequently detected (58.8%). For CYP1A2*1F, Clz dose-normalized (C0/D ratio) was as high as 1.28 ± 0.37 in CC versus 0.67 ± 0.32 ng mL
Identifiants
pubmed: 33731885
doi: 10.1038/s41397-021-00231-x
pii: 10.1038/s41397-021-00231-x
doi:
Substances chimiques
Antipsychotic Agents
0
CYP1A2 protein, human
EC 1.14.14.1
CYP2C19 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP1A2
EC 1.14.14.1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Clozapine
J60AR2IKIC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
551-558Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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