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Pharmacokinetic and Gene Expression Study

ESTIMATED READING TIME: 2 minutes

Increasing Dosage of Leucovorin Results in Pharmacokinetic and Gene Expression Differences When Administered as Two-Hour Infusion or Bolus Injection to Patients with Colon Cancer

Elinor Bexe Lindskog and co-workers at Gothenburg University published a new Pharmacokinetic study of Leucovorin, we supported the project with gene expression profiling measurements.

Summary (from MDPI)
5-fluorouracil (5-FU) is the drug used in almost all chemotherapy regimens for colorectal cancer. To potentiate the drug effect, 5-FU is most often combined with the folate leucovorin (LV). Although 5-FU dosage to some extent is individualized, LV dosage is not. To address the issues of LV dosage and administration this randomized pharmacokinetic study was performed comparing different LV dosages as well as infusion and bolus injection administration regimens. Folate concentrations in blood, tumor, mucosa and resection margins were analyzed as was tissue gene expression. In conclusion, different metabolic mechanisms appear to be induced when LV is administered as two-hour infusion or bolus injection, respectively. To achieve maximal inhibition of the 5-FU target enzyme thymidylate synthase (TS), an excess of the polyglutamated folate metabolite methylenetetrahydrofolate (MeTHF) is needed. Regarding polyglutamation, our results points in favor of the bolus regimen. These results could be used to optimize the effect of 5-FU.

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