Pharmacokinetics of butyric acid derivative with xylitol.
The short chain fatty acids, especially butyric acid salts have interesting biological properties. In some cases, transformed cells can recover a normal phenotype and in animal, butyrate salts increase antitumor resistance. Butyrate may be considered as possibly useful for antitumor therapy. But these products exhibit two essential disadvantages which restrict their clinical use in man: high concentrations required to achieve therapeutic effects and rapid excretion with short half life. In order to optimize the clinical use of butyrate, we studied a n-butyric acid ester obtained with xylitol selected for its physiological and metabolic inertia. Structure determination of tributyryl xylitol was carried out by mass and NMR spectrometry (MW = 344). The low toxicity and the antitumor effects of this ester, especially in association with Corynebacterium parvum and interferon, confirm its therapeutic interest. The slow excretion of this prodrug should make butyrate clinical use easier by preventing extensive systemic metabolism and metabolic side-effects due to cations of butyrate salts.
Desmet
G
G
Laboratoire d'Hormonologie, C.H.U., Amiens, France.
Brazier
M
M
Cerutti
J
J
Chany
C
C
Arnould-Guerin
M L
ML
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002087:Butyrates / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011817:Rabbits; D012513:Sarcoma, Experimental / Q000188:drug therapy; D014993:Xylitol / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology
D000970:Antineoplastic Agents; D002087:Butyrates; D011355:Prodrugs; D014993:Xylitol