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Genetic differences in Native Americans and tacrolimus dosing after kidney transplantation.
- Source :
-
Transplantation proceedings [Transplant Proc] 2013 Jan-Feb; Vol. 45 (1), pp. 137-41. - Publication Year :
- 2013
-
Abstract
- Tacrolimus pharmacokinetics vary due to single nucleotide polymorphisms (SNPs) in metabolizing enzymes and membrane transporters that alter drug elimination. Clinically we observed that Native Americans require lower dosages of tacrolimus to attain trough levels similar to Caucasians. We previously demonstrated that Native Americans have decreased oral clearance of tacrolimus, suggesting that Native Americans may have more variant SNPs and, therefore, altered tacrolimus pharmacokinetic parameters. We conducted 12-hour pharmacokinetic studies on 24 adult Native American kidney transplant recipients on stable doses of tacrolimus for at least 1 month posttransplantation. Twenty-four Caucasian kidney transplant recipients were compared as controls. SNPs encoding the genes for the enzymes (CYP3A4, CYP3A5) and transporters (ABCB1, BCRP, and MRP1) were typed using TaqMan. The mean daily tacrolimus dose in the Native Americans was 0.03 ± 0.02 compared with the Caucasians 0.5 ± 0.3 (mg/kg/d; P = .002), with no significant differences in trough levels, (6.7 ± 3.1 vs 7.4 ± 2.1 ng/dL; P = .4). Many Native Americans, but not Caucasians, demonstrated the 3/*3 - C3435T CC and the *3/*3 -G2677T GG genotype combination previously associated with low tacrolimus dosing. Native Americans required significantly lower tacrolimus doses than Caucasians to achieve similar tacrolimus trough levels, in part due to lower tacrolimus clearance from decreased drug metabolism and excretion.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- ATP Binding Cassette Transporter, Subfamily B
ATP Binding Cassette Transporter, Subfamily B, Member 1 genetics
Adult
Aged
Cohort Studies
Female
Genetic Variation
Humans
Immunosuppressive Agents therapeutic use
Indians, North American
Kidney Failure, Chronic drug therapy
Kidney Failure, Chronic genetics
Male
Middle Aged
Pharmacogenetics
Polymorphism, Single Nucleotide
Tacrolimus therapeutic use
Time Factors
Immunosuppressive Agents pharmacokinetics
Kidney Failure, Chronic ethnology
Kidney Failure, Chronic surgery
Kidney Transplantation methods
Tacrolimus pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2623
- Volume :
- 45
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Transplantation proceedings
- Publication Type :
- Academic Journal
- Accession number :
- 23375287
- Full Text :
- https://doi.org/10.1016/j.transproceed.2012.10.023