Pharmacogenetics and pharmacokinetics of rivaroxaban in patients with atrial fibrillation and chronic kidney disease
Aim . To study the possible relationship between polymorphic variants of ABCB1 ( rs2032582, rs1045642, rs1128503 ), CYP3A5 ( rs776746 ), CYP3A4 ( rs35599367 ) and CYP2J2 ( rs890293 ) genes with residual equilibrium concentrations (Cmin,ss) of rivaroxaban in patients with non-valvular atrial fibrilla...
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Veröffentlicht in: | Rat͡s︡ionalʹnai͡a︡ farmakoterapii͡a︡ v kardiologii 2023-11, Vol.19 (5), p.470-478 |
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Zusammenfassung: | Aim
. To study the possible relationship between polymorphic variants of
ABCB1
(
rs2032582, rs1045642, rs1128503
),
CYP3A5
(
rs776746
),
CYP3A4
(
rs35599367
) and
CYP2J2
(
rs890293
) genes with residual equilibrium concentrations (Cmin,ss) of rivaroxaban in patients with non-valvular atrial fibrillation (AF) and stage 3 and 4 chronic kidney disease (CKD).
Material and methods
. A total of 123 patients 52 to 97 years old (median age, 82 years) with AF in combination with stage 3 and 4 CKD were included in the study. Each patient underwent a pharmacogenetic and pharmacokinetic study.
Results
. Cmin,ss and dose-adjusted concentration (Cmin,ss/D) of rivaroxaban were significantly higher in patients with the
TT
genotype than with the
CT
genotype of the polymorphic variant
rs1045642
of the
ABCB1
gene (Сmin,ss 60,5 [36,7;173] ng/ml and 54,8 [23,1;97,3] ng/ml, respectively, р=0,016; Сmin,ss/D 4,06[2,3;8,1] ng/ml/mg and 2,2 [1,1;4,9] ng/ml/mg, р=0,006). In patients with the
T
allele (
CT
and
TT
genotypes), compared with
CC
genotype carriers, Cmin,ss and Cmin,ss/D were significantly higher (Cmin,ss 60,5 [36,7;173] ng/ml and 45,8 [20,9;82,3] ng/ml, respectively, p=0,029; Cmin,ss/D 4,06 [2,3;8,1] ng/ml/ mg and 2,6 [1,2;4,8] ng/ml/mg, respectively, p=0,014). Also, Cmin,ss and Cmin,ss/D was significantly higher in patients with the
TT
genotype according to the polymorphic variant
rs2032582
of the
ABCB1
gene than in patients with the GG genotype (p=0,02 and р=0,016 respectively). Cmin,ss and Cmin,ss/D in
T
allele (
GT
and
TT
genotypes) carriers were significantly higher than in
T
allele homozygotes (Cmin,ss 57,1 [27,7;106,0] ng/ml versus 37,6 [18,6;61,7] ng/ml respectively, p=0,024; Cmin,ss/D 3,6 [1,7;7,4] ng/ml/mg versus 2,3 [1,1;4,09] ng/ml/mg respectively, p=0,032). Differences in Сmin,ss and Сmin,ss/D of rivaroxaban were detected when comparing
TC
,
CC
and
TT
genotypes of polymorphism rs1128503 of the
ABCB1
gene. When comparing Сmin,ss and Сmin,ss/D of rivaroxaban among carriers of
AG
and
GG
genotypes of the
rs776746
polymorphism of the
CYP3A56986A>G
gene, no significance was detected (p>0,05). Also, no difference in Cmin,ss and Cmin,ss/D was found when comparing carriers of the
CC
and
CT
genotypes of the
rs35599367
polymorphism of the
CYP3A4
gene, and carriers of the
CC
and
AC
genotypes of the
rs890293
polymorphism of the
CYP2J2
gene (p>0,05).
Conclusion
. The carriage of T allele by polymorphic variants
rs1045642
and
rs2032582
of the
ABCB1
gene affects Cmin,ss and |
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ISSN: | 1819-6446 2225-3653 |
DOI: | 10.20996/1819-6446-2023-2970 |