Influence of Absorption, Distribution, Metabolism, and Excretion Genomic Variants on Tacrolimus/Sirolimus Blood Levels and Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Samer K KhaledRyotaro Nakamura

Abstract

Allelic variants of genes implicated in drug absorption, distribution, metabolism, and excretion (ADME) determine the pharmacokinetic variability of many medications and are increasingly recognized as important factors determining the success or failure of medical treatments. Both tacrolimus and sirolimus have narrow therapeutic ranges maintained by therapeutic drug monitoring (TDM). Using an ADME panel that covers >99% of the PharmaADME working group core list (188 single nucleotide polymorphism [SNP] and 12 copy number variant [CNV] assays in 36 pharmacogenetically relevant genes), we studied 177 patients who underwent allogeneic hematopoietic cell transplantation (HCT) using tacrolimus/sirolimus-based graft-versus-host disease (GVHD) prophylaxis. We tested for possible associations between ADME variants and tacrolimus/sirolimus drug levels, concentration/dose (C/D) ratio, and clinical endpoints, including acute GVHD. A total of 62 SNP and 6 CNV assays were evaluable after removing the variants, which were homozygous in (nearly) all samples. For sirolimus, rs2032582 (ABCB1) T-carriers versus non-T-carriers were associated with higher blood levels (P = .01), with similar results for C/D ratio. Generalized estimating equation a...Continue Reading

References

Jan 1, 1989·Pharmacology & Therapeutics·M A McMillan
May 24, 2000·Clinical Therapeutics·H U Meier-Kriesche, B Kaplan
May 23, 2001·Clinical Pharmacokinetics·P E Wallemacq, R K Verbeeck
Apr 28, 2004·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Corey CutlerJoseph H Antin
May 19, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Iain A M MacPheeDavid W Holt
Nov 19, 2004·Springer Seminars in Immunopathology·Frédéric Baron, Rainer Storb
Feb 15, 2005·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Dany AnglicheauEric Thervet
Jan 18, 2006·Seminars in Hematology·James L M Ferrara, Pavan Reddy
Jun 9, 2006·Pharmacology & Therapeutics·Satohiro Masuda, Ken-ichi Inui
Oct 30, 2007·Drug Metabolism and Pharmacokinetics·Kazuhide Iwasaki
Mar 28, 2008·Therapeutic Drug Monitoring·Eric ThervetPhilippe Beaune
Jun 6, 2008·Journal of Clinical Pharmacology·J Andrew WilliamsSteven A Wrighton
Sep 30, 2009·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·David S SnyderStephen J Forman
Aug 18, 2012·Blood·Nathaniel TreisterLeslie Lehmann
Oct 20, 2012·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Sepideh ShayaniRyotaro Nakamura

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Citations

Jun 20, 2018·Clinical Transplantation·Daniel R CalabreseJohn R Greenland
Oct 9, 2018·Transplant Infectious Disease : an Official Journal of the Transplantation Society·Van KieuDoreen Pon
Oct 10, 2019·Expert Opinion on Drug Metabolism & Toxicology·Yuan Gao, Jingjing Ma
Apr 21, 2020·Pharmacogenomics·Jai N Patel, Issam S Hamadeh

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