[Circadian variations of dihydropyrimidine dehydrogenase (DPD) activity in oral mucosa of healthy volunteers].
Dihydropyrimidine 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 drug. Maximal tolerated doses have been highed and anti-tumour activity also. But 30% patients have toxicities expressed by mucositis in oral mucosa.


OBJECTIVE
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.


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 x min(-1) x mg(-1) prot at 10:00 and from 0.07 to 0.16 nmol x min(-1) x 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).


CONCLUSIONS
DPD circadian changes in healthy oral mucosa subjects remained to agree to mononuclear cell, with increase at midnight.
Barrat
M A
MA
Département de prothèses, faculté de chirurgie dentaire de Nice Sophia-Antipolis, avenue Diables-Bleus, 06000, Nice, France. mariebarrat@hotmail.com
Renée
N
N
Mormont
M C
MC
Milano
G
G
Levi
F
F
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics; D002940:Circadian Rhythm; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D004790:Enzyme Induction; D005472:Fluorouracil / Q000493:pharmacokinetics; D006801:Humans; D008875:Middle Aged; D009061:Mouth Mucosa / Q000201:enzymology*; D012016:Reference Values
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil