Preliminary Evidence for Enhanced Thymine Absorption: A Putative New Phenotype Associated With Fluoropyrimidine Toxicity in Cancer Patients

Therapeutic Drug Monitoring
John A DuleyBruce G Charles

Abstract

Chemotherapy for colorectal, head and neck, and breast cancer continues to rely heavily on 5-fluorouracil and its oral prodrug capecitabine. Associations of serious fluoropyrimidine adverse effects have focused on inherited deficiency of the catabolic enzyme, dihydropyrimidine dehydrogenase. However, abnormal dihydropyrimidine dehydrogenase activity accounts for only about one-third of observed toxicity cases. Thus, the cause of most fluorouracil toxicity cases remains unexplained. For this small cohort study, thymine (THY) 250 mg was administered orally to 6 patients who had experienced severe toxicity during treatment with 5FU or capecitabine. Plasma and urine were analyzed for THY and its catabolites dihydrothymine (DHT) and β-ureidoisobutyrate. Of the 6 patients, 2 had decreased THY elimination and raised urinary THY recovery consistent with inherited partial dihydropyrimidine dehydrogenase deficiency, confirmed by DPYD sequencing. Unexpectedly, 3 patients displayed grossly raised plasma THY concentrations but normal elimination profiles (compared with a normal range for healthy volunteers previously published by the authors). DPYD and DPYS sequencing of these 3 patients did not reveal any significant loss-of-activity allel...Continue Reading

References

Jan 1, 1990·Journal of Inherited Metabolic Disease·M BrockstedtR Berger
Jun 1, 1994·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·G MilanoF Demard
May 2, 2003·Nature Reviews. Cancer·Daniel B LongleyPatrick G Johnston
Apr 23, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lori K MattisonRobert B Diasio
Mar 15, 2005·Clinical Therapeutics·Christine M Walko, Celeste Lindley
Jul 6, 2006·Trends in Pharmacological Sciences·Anne E KingStephen A Baldwin
Oct 4, 2006·Clinical Pharmacology and Therapeutics·Guido BocciRomano Danesi
Jan 25, 2008·Pharmacogenetics and Genomics·Holly R ThomasRobert B Diasio
Apr 7, 2010·Biochimica Et Biophysica Acta·André B P van KuilenburgRaoul C M Hennekam
Jul 17, 2013·The Pharmacogenomics Journal·M C van StaverenJ G Maring
Nov 21, 2014·Pharmacogenomics·Johanna SistonenCarlo R Largiadèr
Oct 6, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·John A DuleyBruce G Charles
Nov 10, 2015·British Journal of Clinical Pharmacology·Maurice C van StaverenJan Gerard Maring
Jan 26, 2016·Biochimica Et Biophysica Acta·André B P van KuilenburgCarlo R Largiadèr
Mar 30, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Marta PellicerLuis A López-Fernández

❮ 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.