Single-Nucleotide Polymorphism of CYP3A5 Impacts the Exposure to Tacrolimus in Pediatric Renal Transplant Recipients: A Pharmacogenetic Substudy of the TWIST Trial
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10360991" target="_blank" >RIV/00216208:11130/17:10360991 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/17:10360991
Result on the web
<a href="http://dx.doi.org/10.1097/FTD.0000000000000361" target="_blank" >http://dx.doi.org/10.1097/FTD.0000000000000361</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1097/FTD.0000000000000361" target="_blank" >10.1097/FTD.0000000000000361</a>
Alternative languages
Result language
angličtina
Original language name
Single-Nucleotide Polymorphism of CYP3A5 Impacts the Exposure to Tacrolimus in Pediatric Renal Transplant Recipients: A Pharmacogenetic Substudy of the TWIST Trial
Original language description
Background: The pharmacokinetics of tacrolimus (TAC) and mycophenolic acid (MPA) are highly variable. An impact of singlenucleotide polymorphisms (SNPs) of the genes coding for enzymes and transporters involved in the pharmacokinetics of TAC and/or MPA is intuitively conceivable. Accordingly, we sought to analyze the influence of different SNPs on TAC and MPA exposure in pediatric renal transplant recipients. Methods: A subpopulation of 37 patients (median age: 12.8 years, range 2.2-18.3 years) participating in the TWIST study was included in the analysis of SNPs of CYP3A5, ABCB1 (MDR1), ABCG2, SLCO1B3 (coding for OATP2), ABCC2 (coding for cMOAT), and UGT1/2. TAC trough concentrations and abbreviated area under the concentration-time curves (AUC) of MPA were measured on days 7, 28, 91, and 183 after transplant. Both of these were adjusted to the respective dose the patient received. Results: The allele frequencies of analyzed SNP's were comparable to those reported previously for white populations. Dose-adjusted trough concentrations of TAC were approximately 60% lower in patients with the CYP3A5* 1/*3 allele as compared with the CYP3A5* 3/*3 allele (P = 0.004). Steroid-free patients in CYP3A5* 3/*3 and CYP3A5* 1/* 3 carrier subgroups had comparable dose-adjusted TAC concentrations to the subgroup on steroids (P = 0.13). Patients younger than 10 years had a significantly lower median dose-adjusted TAC C-0 concentration than patients older than 10 years; this age effect was comparable in heterozygous and homozygous CYP3A5 carriers as well as in patients on and off steroid medication. As for MPA, the genetic variability of transporters or enzymes had no impact on dose-adjusted MPA-AUC due to the low allele frequencies. Patients off steroids had a higher dose-adjusted MPA-AUC (0.18 mg.h/L per mg/m(2), 0.012-0.27) compared with patients on steroids (0.12 mg.h.L-1.mg(-1), 0.09-0.19; P = 0.04).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Therapeutic Drug Monitoring
ISSN
0163-4356
e-ISSN
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Volume of the periodical
39
Issue of the periodical within the volume
1
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
21-28
UT code for WoS article
000393966300004
EID of the result in the Scopus database
2-s2.0-85027926967