[Evolution from pharmacokinetics to pharmacogenetics. The example of 5-fluorouracil].
5FU tends to be used more and more frequently; this fact can be explained by its modulation, mainly by folinic acid. Pharmacokinetic follow-up of 5FU with dose adaptation has demonstrated its clinical usefulness by reducing significantly drug side-effects without any impairment in tumor response. Whatever the anticancer drug considered, it is theoretically possible to predict individual capacities for clearing it. This possibility has been explored for 5FU. Among the different tested variables only gender has a determined influence with females showing an average 15% reduction in 5FU clearance as compared to males. Age, hepatic function, nutritional status have no clear influence on 5FU clearance. 5FU catabolism is governed by a key enzymatic step involving dihydropyrimidine dehydrogenase (DPD). Recent case reports have shown that patients with partial or total DPD deficiency shown in lymphocytes were exhibiting severe 5FU related toxicities. A positive and significant correlation has been established between 5FU clearance and DPD activity measured in lymphocytes. This correlation is too weak for allowing individual 5FU dose to be calculated on the basis of lymphocyte DPD activity. Nevertheless DPD determination may allow high risk patients, with partial or total DPD deficiency to be identified.
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Centre Antoine-Lacassagne, Nice, France.
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D005260:Female; D005472:Fluorouracil / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D010599:Pharmacokinetics
D005472:Fluorouracil
Evolution de la pharmacocinétique à la pharmacogénétique. L'exemple du 5-fluorouracile.