Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

K A Birdwell^{1

2}, B Decker³, J M Barbarino⁴, J F Peterson^{2

5}, C M Stein^{2

6}, W Sadee⁷, D Wang⁷, A A Vinks^{8

9}, Y He¹⁰, J J Swen¹¹, J S Leeder¹², Rhn van Schaik¹³, K E Thummel¹⁴, T E Klein⁴, K E Caudle¹⁵, I A M MacPhee¹⁶

Affiliations

¹ Division of Nephrology Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
² Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
³ Division of Nephrology and Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁴ Department of Genetics, Stanford University, Stanford, California, USA.
⁵ Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, USA.
⁶ Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
⁷ Center for Pharmacogenomics, School of Medicine, The Ohio State University, Columbus, Ohio, USA.
⁸ Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁹ Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
¹⁰ Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, Peoples Republic of China.
¹¹ Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
¹² Division of Clinical Pharmacology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
¹³ Department of Clinical Chemistry, Erasmus MC Rotterdam, The Netherlands.
¹⁴ Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
¹⁵ Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹⁶ Institute of Medical and Biomedical Education, Renal Medicine, St. George's, University of London, London, UK.

PMID: 25801146
PMCID: PMC4481158
DOI: 10.1002/cpt.113

Practice Guideline

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

K A Birdwell et al. Clin Pharmacol Ther. 2015 Jul.

. 2015 Jul;98(1):19-24.

doi: 10.1002/cpt.113. Epub 2015 Jun 3.

Authors

Affiliations

¹ Division of Nephrology Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
² Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
³ Division of Nephrology and Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁴ Department of Genetics, Stanford University, Stanford, California, USA.
⁵ Department of Biomedical Informatics, Vanderbilt University, Nashville, Tennessee, USA.
⁶ Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
⁷ Center for Pharmacogenomics, School of Medicine, The Ohio State University, Columbus, Ohio, USA.
⁸ Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁹ Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
¹⁰ Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, Peoples Republic of China.
¹¹ Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
¹² Division of Clinical Pharmacology and Therapeutic Innovation, Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
¹³ Department of Clinical Chemistry, Erasmus MC Rotterdam, The Netherlands.
¹⁴ Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.
¹⁵ Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹⁶ Institute of Medical and Biomedical Education, Renal Medicine, St. George's, University of London, London, UK.

PMID: 25801146
PMCID: PMC4481158
DOI: 10.1002/cpt.113

Abstract

Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).

PubMed Disclaimer

References

1. Finta, C. & Zaphiropoulos, P.G. The human cytochrome P450 3A locus. Gene evolution by capture of downstream exons. Gene 260, 13–23 (2000). - PubMed
1. Kuehl, P. et al Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat. Genet. 27, 383–391 (2001). - PubMed
1. van Schaik, R.H. , van der Heiden, I.P. , van den Anker, J.N. & Lindemans, J. CYP3A5 variant allele frequencies in Dutch caucasians. Clin. Chem. 48, 1668–1671 (2002). - PubMed
1. Thompson, E.E. , Kuttab‐Boulos, H. , Witonsky, D. , Yang, L. , Roe, B.A. & Di Rienzo, A. CYP3A variation and the evolution of salt‐sensitivity variants. Am. J. Hum. Genet. 75, 1059–1069 (2004). - PMC - PubMed
1. Bowman, L.J. & Brennan, D.C. The role of tacrolimus in renal transplantation. Expert Opin. Pharmacother. 9, 635–643 (2008). - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

Affiliations

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical