The effect of MDR1 (ABCB1) polymorphism on the pharmacokinetic of tacrolimus in Turkish renal transplant recipients.
There is marked interindividual variability in trough blood levels of tacrolimus (TRL) following standard dosing. TRL is a substrate for P-glycoprotein (P-gp), the product of the multidrug resistance-1 (MDR1)(ABCB1) gene. P-gp acts as a membrane efflux pump, which affects TRL absorption from the gut. Some of the single nucleotide polymorphisms (SNP) of ABCB1 gene are associated with pharmacokinetic characteristics of TRL. The objective of this study was to determine the role of ABCB1 C3435T polymorphism on TRL dose requirements, trough values and dose-adjusted trough TRL concentrations among Turkish renal transplant recipients. Renal transplant recipients receiving TRL (n=92) were genotyped for ABCB1. TRL daily doses, trough concentrations, dose-adjusted trough concentrations, demographic features, and clinical data were obtained at 1, 6, and 12 months after renal transplantation. The frequency of the ABCB1 3435 CC genotype was 30.4%, whereas 47.8% of patients were 3435 CT and 21.7% of patients were 3435 TT. TRL daily doses were significantly lower among patients with the 3435 TT genotype at months 1 and 6. At 6 and 12 months after transplantation patients who were homozygous for the ABCB1 3435 CC showed significantly lower dose-adjusted trough TRL concentrations compared with subjects of 3435 TT and CT genotypes. Knowledge of ABCB1 genotype may be useful to adjust the optimal dose of TRL in transplant patients, thereby rapidly achieving target concentrations.
Akbas
S H
SH
Central Laboratory, Akdeniz University, Faculty of Medicine, Antalya, Turkey. halideakbas@akdeniz.edu.tr
Bilgen
T
T
Keser
I
I
Tuncer
M
M
Yucetin
L
L
Tosun
O
O
Gultekin
M
M
Luleci
G
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D003404:Creatinine / Q000097:blood; D019450:Genes, MDR; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008657:Metabolic Clearance Rate; D011110:Polymorphism, Genetic; D016559:Tacrolimus / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014421:Turkey
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus