Desmet G, Brazier M, Cerutti J, Chany C, Arnould-Guerin M L
Laboratoire d'Hormonologie, C.H.U., Amiens, France.
Eur J Drug Metab Pharmacokinet. 1991;Spec No 3:348-51.
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.
短链脂肪酸，尤其是丁酸盐具有有趣的生物学特性。在某些情况下，转化细胞可恢复正常表型，在动物中，丁酸盐可增强抗肿瘤抵抗力。丁酸盐可被认为可能对抗肿瘤治疗有用。但这些产品存在两个基本缺点，限制了它们在人体中的临床应用：达到治疗效果所需的浓度高，且半衰期短、排泄快。为了优化丁酸盐的临床应用，我们研究了一种用木糖醇获得的正丁酸酯，选择木糖醇是因其生理和代谢惰性。通过质谱和核磁共振光谱法（分子量 = 344）对三丁酰木糖醇进行了结构测定。该酯的低毒性和抗肿瘤作用，尤其是与短小棒状杆菌和干扰素联合使用时，证实了其治疗价值。这种前药的缓慢排泄应能通过防止丁酸盐阳离子引起的广泛全身代谢和代谢副作用，使丁酸盐的临床应用更容易。
