Impact of ATP-binding cassette, subfamily B, member 1 pharmacogenetics on tacrolimus-associated nephrotoxicity and dosage requirements in paediatric patients with liver transplant

Expert Opinion on Drug Safety
Ahmed F Hawwa, James C McElnay

Abstract

Tacrolimus is the most commonly used immunosuppressive agent following solid-organ transplantation in children. Its clinical use, however, is complicated by side effects (mainly nephrotoxicity), narrow therapeutic index and pharmacokinetic variability which can result in an increased risk of treatment failure or toxicity. Studies examining interindividual differences in the expression of the ABCB1 (ATP-binding cassette, subfamily B, member 1) gene (which encodes the drug transporter, P-gp) and its genetic polymorphisms have attempted to elucidate variations in tacrolimus response and disposition in children. This review explores pharmacogenetic knowledge developed over the last decade regarding the impact of ABCB1 polymorphisms on tacrolimus toxicity and dosage requirements in children. A better understanding of the role of ABCB1 genetic polymorphisms (and corresponding haplotypes) and ABCB1 expression levels in various tissues and organs on tacrolimus outcomes in children with liver transplant. Pharmacogenetics offers significant potential for optimising tacrolimus use. ABCB1 donor genotypes and ABCB1 expression level in the intestine and leukocytes may be useful in dosage selection. Large prospective studies are, however, req...Continue Reading

References

Feb 1, 1991·Transplantation Proceedings·R AyresJ Neuberger
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A T FojoI Pastan
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·F ThiebautM C Willingham
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan
Dec 1, 1995·Clinical Pharmacokinetics·R VenkataramananT Starzl
Dec 8, 1998·European Journal of Drug Metabolism and Pharmacokinetics·P E WallemacqN A Undre
Oct 16, 1999·Journal of Controlled Release : Official Journal of the Controlled Release Society·L Z BenetV J Wacher
Jan 11, 2000·Clinical Pharmacokinetics·S N de WildtJ N van den Anker
Mar 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·S HoffmeyerU Brinkmann
Jan 13, 2001·Clinical Chemistry and Laboratory Medicine : CCLM·Z Tolou-GhamariJ M Tredger
Apr 11, 2001·Journal of the American College of Surgeons·Y SugawaraK Hashizume
May 22, 2001·Journal of Clinical Pharmacology·R VenkataramananA Shaked
Aug 15, 2001·Clinical Pharmacology and Therapeutics·R B KimG R Wilkinson
Sep 29, 2001·Advanced Drug Delivery Reviews·L Z Benet, C L Cummins
Feb 28, 2002·The Journal of Pharmacology and Experimental Therapeutics·Carolyn L CumminsLeslie Z Benet
Jun 29, 2002·Journal of the American Society of Nephrology : JASN·Michael SiegsmundHiltrud Brauch
Feb 7, 2003·The New England Journal of Medicine·William E Evans, Howard L McLeod
Mar 19, 2003·Lancet·Helen M ColhounGeorge Davey Smith
Mar 22, 2003·The Journal of Pharmacology and Experimental Therapeutics·Carolyn L CumminsLeslie Z Benet
Jul 2, 2003·Pharmacogenomics·Toshiyuki SakaedaKatsuhiko Okumura
Aug 2, 2003·Pharmacogenetics·Deanna L KroetzUNKNOWN Pharmacogenetics of Membrane Transporters Investigators
Sep 5, 2003·The New England Journal of Medicine·Akinlolu O OjoRobert M Merion
Nov 25, 2003·The Journal of Pharmacology and Experimental Therapeutics·Yvonne Y LauLeslie Z Benet
Jan 30, 2004·Clinical Pharmacology and Therapeutics·Catia MarzoliniRichard B Kim
Mar 26, 2004·Transplantation Proceedings·M H KapturczakB Kaplan
Jul 2, 2004·Therapeutic Drug Monitoring·Uwe Christians

❮ Previous
Next ❯

Citations

Sep 21, 2011·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Violette GijsenSaskia N de Wildt
Jun 7, 2013·British Journal of Clinical Pharmacology·Mariam H Abdel JalilJames C McElnay
Aug 6, 2019·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Dongdong WangZhiping Li

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.