Dihydropyrimidine dehydrogenase activity in a Korean population

Area of Science:

• Pharmacology
• Biochemistry
• Genetics

Background:

• Dihydropyrimidine dehydrogenase (DPD) is crucial for metabolizing 5-fluorouracil, a widely used chemotherapy drug.
• DPD activity exhibits significant inter-individual variability, influencing drug efficacy and toxicity.
• Understanding DPD activity is key to personalizing 5-fluorouracil treatment regimens.

Purpose of the Study:

• To investigate the DPD enzyme activity in peripheral blood mononuclear cells of healthy Korean subjects.
• To establish reference ranges for DPD activity in this population.
• To compare DPD activity in Koreans with previously reported data from other ethnic groups.

Main Methods:

• Collected peripheral blood mononuclear cells from 114 healthy Korean volunteers.
• Quantified DPD enzyme activity using a spectrophotometric assay.
• Analyzed DPD activity data for distribution, mean, variability, and sex-based differences.

Main Results:

• DPD activity in healthy Korean subjects followed a unimodal distribution with a mean of 0.28 ± 0.16 nmol/min/mg protein.
• A substantial 13-fold inter-individual variability in DPD activity was observed (range: 0.06–0.80 nmol/min/mg protein).
• DPD activity was approximately 13% lower in women (0.26 ± 0.14) compared to men (0.30 ± 0.16).
• Observed DPD activity levels were higher than those reported in French and white American populations.

Conclusions:

• Significant inter-individual and sex-based variations in DPD activity exist in the Korean population.
• The higher DPD activity in Koreans suggests potential differences in 5-fluorouracil pharmacokinetics and toxicity compared to other populations.
• These findings underscore the importance of DPD activity assessment for optimizing 5-fluorouracil chemotherapy in Korean patients.