Effects of a bolus injection of 5-fluorouracil on dihydropyrimidine dehydrogenase activity in rats receiving continuous infusion of 5-fluorouracil

Abstract

A bolus injection suppresses hepatic DPD activity and its effects are dependent on dosage, resulting in slower elimination of 5-FU from the blood and contributing to long-term systemic exposure to 5-FU.

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

“…However, the degradation rate of 5‐FU could not be accurately evaluated due to the presence of 5‐FU, which was metabolized from capecitabine. Alternatively, to verify the hypothesis, the plasma UH 2 /Ura ratio was evaluated after the administration of capecitabine plus a bolus injection of 5‐FU, which suppresses the DPD activity and maintains a low plasma UH 2 /Ura ratio (Kobuchi et al, ). There was a decrease in the plasma UH 2 /Ura ratio; however, the ratio rapidly recovered to its initial level (Figure b).…”

“…Male Wistar rats aged 10 weeks were supplied by Nippon SLC Co., Ltd (SLC, Hamamatsu, Japan). To investigate the relationship between the plasma UH 2 /Ura ratio and DPD activity, the suppression of DPD activity by a bolus injection of 5‐FU was employed, as described in our previous study (Kobuchi et al, ). The rats were divided into two groups (n = 4 in each group) as follows: 180 mg/kg capecitabine (22.5 mg/ml in 1% carboxymethyl‐cellulose sodium in distilled water) was orally administered with a 2 min bolus injection of saline or 60 mg/kg 5‐FU (10 mg/ml in saline) into the external right jugular vein at a predetermined time of the day.…”