Relationship between pharmacokinetics of 5-FU in plasma and in saliva, and toxicity of 5-fluorouracil/folinic acid.
BACKGROUND
Dose adaptation based on pharmacokinetic parameters has been shown to decrease toxicity of some 5-fluorouracil(5-FU)-based continuous infusion regimens.


METHODS
In the present study the relationship between 5-FU pharmacokinetics in plasma and in saliva, and toxicity was investigated in 40 patients receiving the combination of 5-FU 425 mg/m2 and folinic acid 20 mg/m2 daily during 5 consecutive days according to the Mayo-regimen.


RESULTS
The overall non-hematological and hematological toxicity, as well as mucositis only, were not statistically significant related to the area-under-the-curve in plasma (AUCp) or in saliva (AUCs), nor to the maximum concentration measured in plasma (Cmaxp) or in saliva (Cmaxs). Although statistically significant, the correlation between the AUCp and AUCs was relatively low, implying that salivary pharmacokinetics are not accurately predictive of plasma pharmacokinetics.


CONCLUSIONS
The conclusion of this study is that the application of pharmacokinetic parameters is not appropriate for identification of patients at risk for developing toxicity from treatment with 5-FU according to the Mayo-regimen.
Jansman
Frank G A
FG
Department of Clinical Pharmacy, Isala Klinieken, Groot Wezenland 20, P.O. Box 10500, 8000 GM Zwolle, The Netherlands. f.g.a.jansman@isala.nl
Coenen
Jules L L M
JL
De Graaf
Jacques C
JC
Tobi
Hilde
H
Sleijfer
Dirk T
DT
Brouwers
Jacobus R B J
JR
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000378:metabolism*
D002955:Leucovorin; D005472:Fluorouracil