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Capecitabine is a 5-fluorouracil (5-FU) derivative that is widely used in the treatment of colorectal cancer. The plasma ratio of dihydrouracil (UH ) to uracil (Ura) is expected to gain relevance as an indirect-response biomarker to estimate the activity of dihydropyrimidine dehydrogenase (DPD). The latter is a rate-limiting enzyme in the catabolism of 5-FU in the capecitabine-based regimen. However, the relationship between the pharmacokinetics of capecitabine and the plasma UH /Ura ratio is still unknown. In this study, we evaluated the time-course alterations of the plasma UH /Ura ratio in rats treated with 180 mg/kg capecitabine. The molar ratio tended to increase within 1.5 h (1.85 ± 0.76 at 1.5 h after administration of capecitabine) and gradually recovered to its initial level (1.00 ± 0.46). The results of the current study suggest that the plasma UH /Ura ratio temporarily increases following administration of capecitabine, possibly related to the DPD activity levels. The plasma UH /Ura ratio might assist in monitoring the alteration of DPD activity levels in capecitabine treatments.
This article was published in the following journal.
Name: Biopharmaceutics & drug disposition
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Healthy volunteer food-effect study to determine the effect of food on uracil and dihydrouracil levels in plasma
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An enzyme that catalyzes the oxidation of 5,6-dihydrouracil to URACIL using NAD as a cofactor. This enzyme also plays a role in the catabolism of the antimetabolite 5-FLUOROURACIL.
An oxidoreductase involved in pyrimidine base degradation. It catalyzes the catabolism of THYMINE; URACIL and the chemotherapeutic drug, 5-FLUOROURACIL.
The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases.
An enzyme that catalyzes the HYDROLYSIS of the N-glycosidic bond between sugar phosphate backbone and URACIL residue during DNA synthesis.
Nitrogen mustard derivative of URACIL. It is a alkylating antineoplastic agent that is used in lymphatic malignancies, and causes mainly gastrointestinal and bone marrow damage.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...