Minguez F, Chiu M L, Lima J E, Nique R, Prieto J
Department of Microbiology, School of Medicine, Universidad Complutense, Madrid, Spain.
J Antimicrob Chemother. 1994 Jul;34(1):93-100. doi: 10.1093/jac/34.1.93.
Exposure times and serum concentrations in humans after treatment with multiple doses of fluconazole have been studied to measure: (a) the postantifungal effect (PAFE) on Candida albicans, at two concentrations of the drug in the presence or absence of 10% human serum; (b) the activity of low concentrations of the drug on yeasts previously exposed to fluconazole with or without 10% human serum; and (c) the effect of fluconazole pretreatment on the fungicidal activity of leucocytes and serum against C. albicans. Fluconazole showed no PAFE against C. albicans between -0.1 and -0.7 h, but when the assays were performed in the presence of serum, concentration dependent PAFEs were obtained (1.1 h-3.6 h). Pretreated yeasts were more susceptible than untreated yeasts to low concentrations of the drug. The decrease in growth was dependent on the concentration used in pretreatment. Growth delay was also more marked when the yeast cells were tested in the presence of serum. Pretreatment of the growing C. albicans cells with fluconazole increased their vulnerability to killing by leucocytes mainly in the first hour (P < 0.05). These results could partially explain why fluconazole has more activity in vivo than in vitro.
研究了多次服用氟康唑后人体的暴露时间和血清浓度，以测定：(a) 在有或无10%人血清存在的情况下，两种药物浓度对白色念珠菌的抗真菌后效应(PAFE)；(b) 低浓度药物对先前暴露于氟康唑的酵母的活性，有或无10%人血清；以及(c) 氟康唑预处理对白细胞和血清针对白色念珠菌的杀菌活性的影响。氟康唑在-0.1至-0.7小时之间对白色念珠菌无PAFE，但在血清存在下进行测定时，可获得浓度依赖性PAFE(1.1小时至3.6小时)。预处理的酵母比未处理的酵母对低浓度药物更敏感。生长的降低取决于预处理中使用的浓度。当在血清存在下测试酵母细胞时，生长延迟也更明显。用氟康唑预处理生长中的白色念珠菌细胞，主要在第一个小时增加了它们对白细胞杀伤的易感性(P<0.05)。这些结果可以部分解释为什么氟康唑在体内比在体外具有更强的活性。
