PHARMACOLOGICAL STUDIES WITH 5-FLUOROCYTOSINE
PHARMACOLOGICAL STUDIES WITH 5-FLUOROCYTOSINE
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DOI：
10.1128/aac.1.6.476
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发表时间：
1972-01-01
影响因子：
4.9
通讯作者：
BENNETT, JE
中科院分区：
文献类型：
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作者：
BLOCK, ER;BENNETT, JE
描述了一种用于5-氟胞嘧啶（5-FC）的柱管板生物测定法，其允许在存在阿替霉素B的情况下测定生物流体中的5-FC浓度。使用该测定法，我们测定了12例单次给药后患者和8例以6小时间隔（4至120天）每日接受5-FC治疗的患者的血清浓度。早在0.5小时就可在血清中检测到药物，并且无论肾功能如何，给药后24小时即可测量浓度。峰浓度出现在首次给药后6小时，但在所有接受至少4天治疗的患者中，在给药后1 - 2小时观察到峰浓度。轻度至中度肾损害导致一组8例患者在3种不同给药方案下血清中5-FC峰浓度显著升高。研究了5例患者在阿替霉素B诱导的肾功能不全前后的情况。随着肾功能的变化，峰浓度从14%增加至142%。在兔子中进行的平行研究证实了我们患者的结果。10只家兔急性肾功能衰竭后5-FC在血清中的半衰期由3.35 ± 0.27小时增加到24.63 ± 0.70小时。5例患者脑脊液中5-FC浓度范围为17 - 62 μg/ml，为同时测定的血清浓度的74.4 ± 5.6%。肾功能对脑脊液中5-FC浓度的影响与血清中观察到的相似。
A cylinder plate bioassay for 5-fluorocytosine (5-FC) is described which permits determination of 5-FC concentrations in biological fluids in the presence of amphotericin B. Using this assay, we determined serum concentrations in 12 patients after a single dose of drug and in 8 patients receiving daily 5-FC at 6-hr intervals (4 to 120 days). Drug was detectable in serum as early as 0.5 hr and concentrations were measurable as long as 24 hr after a dose, regardless of renal function. Peak concentrations occurred 6 hr after the initial drug dose, but were seen between 1 and 2 hr after a dose in all patients receiving a minimum of 4 days of therapy. Mild to moderate renal impairment produced marked increases in peak 5-FC concentrations in the serum of a group of eight patients on three different dosage schedules. Five patients were studied before and after amphotericin B-induced renal insufficiency. Peak concentrations increased from 14 to 142% concomitant with the change in renal function. Parallel studies in rabbits confirmed the results in our patients. 5-FC half-life in the serum of 10 rabbits increased from 3.35 ± 0.27 to 24.63 ± 0.70 hr after experimentally induced acute renal failure. Concentrations of 5-FC in the cerebrospinal fluid of five patients ranged from 17 to 62 μg/ml and were 74.4 ± 5.6% of simultaneously determined serum concentrations. The effect of renal function on 5-FC concentrations in cerebrospinal fluid was similar to that seen with serum.