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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Acenocoumarol sensitivity and pharmacokinetic characterization of CYP2C9 *5/*8,*8/*11,*9/*11 and VKORC1 2 in black African healthy Beninese subjects
European Journal of Drug Metabolism and Pharmacokinetics, Volume 37, No. 2, Year 2012
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Description
This study aimed at investigating the contribution of CYP2C9 and VKORC1 genetic polymorphisms to inter-individual variability of acenocoumarol pharmacokinetics and pharmacodynamics in Black Africans from Benin. Fifty-one healthy volunteers were genotyped for VKORC1 1173C>T polymorphism. All of the subjects had previously been genotyped for CYP2C9*5, CYP2C9*6, CYP2C9*8, CYP2C9*9 and CYP2C9*11 alleles. Thirty-six subjects were phenotyped with a single 8 mg oral dose of acenocoumarol by measuring plasma concentrations of (R)- and (S)-Acenocoumarol 8 and 24 h after the administration using chiral liquid-chromatography tandem massspectrometry. International normalized ratio (INR) values were determined prior to and 24 h after the drug intake. The allele frequency of VKORC1 variant (1173C>T) was 1.96% (95% CI 0.0-4.65%). The INR values did not show statistically significant difference between the CYP2C9 genotypes, but were correlated with body mass index and age at 24 h post-dosing (P < 0.05). At 8 h post dose, the (S)-Acenocoumarol concentrations in the CYP2C9*5/*8 and CYP2C9*9/*11 genotypes were about 1.9 and 5.1 fold higher compared with the CYP2C9*1/*1 genotype and 2.2- and 6.0-fold higher compared with the CYP2C9*1/*9 group, respectively. The results indicated that pharmacodynamic response to acenocoumarol is highly variable between the subjects. This variability seems to be associated with CYP2C9*5/*8 and *9/*11 variant and demographic factors (age and weight) in Beninese subjects. Significant association between plasma (S)-Acenocoumarol concentration and CYP2C9 genotypes suggested the use of (S)-Acenocoumarol for the phenotyping purpose. Larger number of subjects is needed to study the effect of VKORC1 1173C>T variant due to its low frequency in Beninese population. © Springer-Verlag France 2011.
Authors & Co-Authors
Allabi, Aurel Constant E.
Benin, Cotonou, Bénin
Faculté Des Sciences de la Santé de Cotonou
Horsmans, Y.
Belgium, Louvain-la-neuve
Université Catholique de Louvain
Alvarez, Jean Claude
France, Versailles
Université de Versailles Saint-quentin-en-yvelines
Bigot, André K.
Benin, Porto
Uac
Verbeeck, Roger K.
Belgium, Louvain-la-neuve
Université Catholique de Louvain
South Africa, Grahamstown
Rhodes University
Yasar, Ümit
Turkey, Ankara
Hacettepe Üniversitesi
Gala, Jean Luc
Belgium, Louvain-la-neuve
Université Catholique de Louvain
Statistics
Citations: 7
Authors: 7
Affiliations: 6
Identifiers
Doi:
10.1007/s13318-011-0056-7
ISSN:
03787966
Research Areas
Genetics And Genomics
Health System And Policy
Study Design
Cross Sectional Study
Study Locations
Benin