Abstract
Dehydropyrimidine dehydrogenase (DPD) is the rate limiting enzyme of 5-fluoro-uracil (5-FU) catabolism. DPD rhythmicity, peak at 1:00 is an important determinant of 5-FU tolerability and has practical implications for the pattern of chronomodulated delivery of the drog. Maximal tolerated doses have been highed and anti-tumour activityalso. But 30% patients have toxicities expressed by mucositis in oral mucosa. Purpose. – Titrate DPD activity in oral mucosa in healthy subjects, in oral mucosa which is the target of 5-FU, at 10:00 and midnight could help to understand toxicities in patients. Subjects and methods. – Eight healthy subjects participated (information note signed by patients). One oral mucosa sample was drawn at 10:00 and an other at midnight. DPD activity was analyzed by a H.P.L.C. method. Results. – DPD activity in oral mucosa varied from 0.004 to 0.13 nmol min –1 mg –1 prot at 10:00 and from 0.07 to 0.16 nmol min –1 mg –1 prot at midnight, with a 30% average relative increase from morning to midnight (range: –20% to +100%; statistical significant difference with P <0.073). Conclusion. – DPD circadian changes in healthy oral mucosa subjects remained to agree to mononuclear cell, with increase at midnight.
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