Association between the pharmacokinetics of capecitabine and the plasma dihydrouracil to uracil ratio in rat: a surrogate biomarker for dihydropyrimidine dehydrogenase activity.

07:00 EST 28th December 2018 | BioPortfolio

Summary of "Association between the pharmacokinetics of capecitabine and the plasma dihydrouracil to uracil ratio in rat: a surrogate biomarker for dihydropyrimidine dehydrogenase activity."

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.


Journal Details

This article was published in the following journal.

Name: Biopharmaceutics & drug disposition
ISSN: 1099-081X


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Medical and Biotech [MESH] Definitions

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.

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