5-氟胞嘧啶的临床应用

来源 :华西药学杂志 | 被引量 : 0次 | 上传用户:xiaokexiaoai1314
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5-氟胞嘧啶(5-Flucylosine) (简称5-FC)是1957年合成的一种抗癌剂,但药理研究表明,5-FC并无抗癌活性,1964年却发现有抗真菌活性。随着真菌病的日益增多,5-FC也在临床上得到广泛应用。抗菌谱某些细菌如肠杆菌,由于能把5-FC脱氨基生成5-氟尿嘧啶,所以对5-FC敏感。从未经治疗的93%念珠菌病及96%隐球菌病患者中,分离的多数菌株对5-FC敏感。据称,93%白色念珠菌为≥25μg/ml的5-FC血药浓度所抑制。光滑隐球菌的分离物一般对5-FC敏感,但5-7%分离物有耐药性。在体内外测定中,致病真菌一般耐受5-FC,但瓶霉菌、分支孢子菌、孢子丝菌、曲霉菌及拟球酵母对5-FC敏感。5μg/ml5-FC对着色真菌有抑菌作用某些嘌呤和嘧啶化合物能抑制5-FC的抗曲霉菌作用;二性霉素能增加5-FC抗念珠菌、新型隐球菌和曲霉菌的活性;克霉唑则增加5-FC和二性霉素抗白色念球菌、球拟酵母的活性吸收和代谢5-FC由胃肠道吸收。口服2g 5-FC,在2-4小时内最高血浆浓度可达30-40μg/ml;静脉注射上述剂量能更迅速达到同样血药浓度。90%的药物以未被代谢的形式从尿中排出。5-FC广泛分布于组织和体液中,在脑脊液中的浓度为血浆浓度的75%,腹腔液为100%,水状液为20%,支气管分泌物为76%。 5-Flucytosine (5-FC) is an anti-cancer agent synthesized in 1957. However, pharmacological studies have shown that 5-FC has no anticancer activity and antifungal activity was found in 1964. With the increasing number of fungal diseases, 5-FC is also widely used in clinical practice. Antibacterial spectrum Some bacteria, such as Enterobacter, are 5-FC sensitive due to their ability to deaminate 5-FC to 5-fluorouracil. From 93% of never treated candidiasis and 96% of cryptococcal patients, most isolates were 5-FC sensitive. 93% of Candida albicans is said to be inhibited by 5-FC plasma concentrations of> 25 [mu] g / ml. Isolates of C. difficile are generally 5-FC sensitive, but 5-7% of isolates are resistant. Pathogenic fungi generally tolerated 5-FC in vitro and in vivo, but 5-FC was sensitive to Corynebacterium, Pseudomonas, Sporotrichosis, Aspergillus and Pichia sp. 5μg / ml 5-FC has antimicrobial activity against colored fungi Some purine and pyrimidine compounds inhibit 5-FC anti-Aspergillus role; amphotericin can increase 5-FC anti-Candida, Cryptococcus neoformans and Aspergillus activity ; Clotrimazole increased 5-FC and amphotericin against Candida albicans, the yeast activity of yeast absorption and metabolism of 5-FC absorbed by the gastrointestinal tract. Oral 2g 5-FC, the highest in 2-4 hours the plasma concentration of up to 30-40μg / ml; intravenous injection of these doses can achieve the same plasma concentration more rapidly. Ninety percent of the drug is excreted from the urine in an unmetabolized form. 5-FC is widely distributed in tissues and body fluids in cerebrospinal fluid in concentrations of 75% of plasma, 100% of peritoneal fluids, 20% of aqueous fluids and 76% of bronchial secretions.
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