BACKGROUND: Polymorphisms in genes encoding for drug-metabolizing enzymes and drug transporters are among multiple factors that modulate the pharmacokinetic variability of tacrolimus (TAC) and sirolimus (SRL). This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) on TAC and SRL dose-adjusted concentrations (C0/D) in stable kidney transplant recipients. METHODS: This is an exploratory and prospective study, which includes 46 stable kidney transplant recipients. These patients were monitored from the 3rd to the 24th month after transplantation. The SRL group consisted of 25 patients receiving TAC, prednisone (PRED), and mycophenolate sodium (MPS), which were converted from TAC to SRL at 3rd month after transplantation. The TAC group consisted of 21 patients who underwent treatment with TAC, PRED, and MPS. Both groups were genotyped for CYP3A4 rs2242480 (g.20230G>A), CYP3A5 rs15524 (g.31611C>T), CYP2C8 rs10509681 (c.1196A>G) and ABCB1 rs1045642 (c.3435C>T), rs1128503 (c.1236C>T), and rs2032582 (c.2677G>T/A) polymorphisms. RESULTS: In the TAC group, CYP3A4 rs2242480 A allele carriers were associated with lower TAC C0/D. For CYP3A5 rs15524 SNP, C0/D was higher among patients carrying TT genotype when compared with CT and CC genotype carriers in the SRL and, more consistently, in the TAC groups. For ABCB1 rs1045642 SNP, TT genotype was associated with reduced SRL C0/D, but only at month 15. CONCLUSIONS:CYP3A4 rs2242480 and CYP3A5 rs15524 SNPs resulted in significant changes in SRL and TAC C0/D at different times after transplantation.
RCT Entities:
BACKGROUND: Polymorphisms in genes encoding for drug-metabolizing enzymes and drug transporters are among multiple factors that modulate the pharmacokinetic variability of tacrolimus (TAC) and sirolimus (SRL). This study aimed to evaluate the influence of single nucleotide polymorphisms (SNPs) on TAC and SRL dose-adjusted concentrations (C0/D) in stable kidney transplant recipients. METHODS: This is an exploratory and prospective study, which includes 46 stable kidney transplant recipients. These patients were monitored from the 3rd to the 24th month after transplantation. The SRL group consisted of 25 patients receiving TAC, prednisone (PRED), and mycophenolate sodium (MPS), which were converted from TAC to SRL at 3rd month after transplantation. The TAC group consisted of 21 patients who underwent treatment with TAC, PRED, and MPS. Both groups were genotyped for CYP3A4rs2242480 (g.20230G>A), CYP3A5rs15524 (g.31611C>T), CYP2C8rs10509681 (c.1196A>G) and ABCB1rs1045642 (c.3435C>T), rs1128503 (c.1236C>T), and rs2032582 (c.2677G>T/A) polymorphisms. RESULTS: In the TAC group, CYP3A4rs2242480 A allele carriers were associated with lower TAC C0/D. For CYP3A5rs15524 SNP, C0/D was higher among patients carrying TT genotype when compared with CT and CC genotype carriers in the SRL and, more consistently, in the TAC groups. For ABCB1rs1045642 SNP, TT genotype was associated with reduced SRL C0/D, but only at month 15. CONCLUSIONS:CYP3A4rs2242480 and CYP3A5rs15524 SNPs resulted in significant changes in SRL and TAC C0/D at different times after transplantation.
Authors: Deirdre Hahn; Elisabeth M Hodson; Lorraine A Hamiwka; Vincent Ws Lee; Jeremy R Chapman; Jonathan C Craig; Angela C Webster Journal: Cochrane Database Syst Rev Date: 2019-12-16
Authors: Laith N Al-Eitan; Islam M Al-Dalalah; Mohamed M Mustafa; Mansour A Alghamdi; Afrah K Elshammari; Wael H Khreisat; Mohammed N Al-Quasmi; Hanan A Aljamal Journal: Pharmgenomics Pers Med Date: 2019-09-04
Authors: Alison E Fohner; Rachel Dalton; Kasse Skagen; Konner Jackson; Katrina G Claw; Scarlett E Hopkins; Renee Robinson; Burhan A Khan; Bhagwat Prasad; Erin G Schuetz; Deborah A Nickerson; Timothy A Thornton; Denise A Dillard; Bert B Boyer; Kenneth E Thummel; Erica L Woodahl Journal: Clin Transl Sci Date: 2021-01-27 Impact factor: 4.689