Vermes András, Guchelaar Henk-Jan, van Kuilenburg Andre B P, Dankert Jacob
Department of Clinical Pharmacy, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Fundam Clin Pharmacol. 2002 Feb;16(1):39-47. doi: 10.1046/j.1472-8206.2002.00064.x.
The aim of this study is to investigate whether fluorouracil (5-FU) could be responsible for bone-marrow depression occurring in fluorocytosine (5-FC) treated patients. Six 5-FC treated patients were included in this pilot study. Toxicity was monitored by means of thrombocyte and leucocyte counts. 5-FC and 5-FU serum levels were measured using a high-performance liquid chromatography (HPLC) assay that allows simultaneous determination of both compounds. The amounts of 5-FU in the 34 available serum samples remained below the limit of quantitation (< 0.05 mg/L), whereas 5-FC levels could be detected in all samples. Instead, low levels of the 5-FU catabolite alpha-fluoro-beta-alanine (FBAL) were detected in several of the investigated serum samples. In case of three patients thrombocyte counts remained within the normal range during 5-FC treatment, whereas one patient developed thrombocytopenia (50 x 10(9) thrombocytes/L) during therapy. Furthermore, one patient developed leucocytopenia (2.6 x 10(9) leucocytes/L) during 5-FC therapy, whereas the remaining five patients were suffering from leucocytosis prior to 5-FC therapy. In conclusion, we found nondetectable 5-FU serum concentrations (< 0.05 mg/L) in ICU patients treated with intravenous 5-FC, making it unlikely that 5-FC-associated toxicity results from 5-FU exposure in patients receiving intravenous 5-FC therapy. These findings may be explained by the fact that our patients received 5-FC intravenously instead of orally, therefore not allowing active conversion of 5-FC to 5-FU by the human intestinal microflora.
本研究的目的是调查氟尿嘧啶（5-FU）是否可能是接受氟胞嘧啶（5-FC）治疗的患者发生骨髓抑制的原因。本初步研究纳入了6例接受5-FC治疗的患者。通过血小板和白细胞计数监测毒性。使用可同时测定这两种化合物的高效液相色谱（HPLC）分析法测量5-FC和5-FU的血清水平。在34份可用血清样本中，5-FU的含量均低于定量限（<0.05 mg/L），而所有样本中均能检测到5-FC水平。相反，在几份被调查的血清样本中检测到低水平的5-FU分解代谢产物α-氟-β-丙氨酸（FBAL）。在3例患者中，5-FC治疗期间血小板计数保持在正常范围内，而1例患者在治疗期间出现血小板减少（50×10⁹个血小板/L）。此外，1例患者在5-FC治疗期间出现白细胞减少（2.6×10⁹个白细胞/L），而其余5例患者在5-FC治疗前患有白细胞增多症。总之，我们发现在接受静脉注射5-FC治疗的ICU患者中，5-FU血清浓度无法检测到（<0.05 mg/L），这使得接受静脉注射5-FC治疗的患者中5-FC相关毒性不太可能是由5-FU暴露引起的。这些发现可能是由于我们的患者接受的是静脉注射5-FC而非口服，因此人体肠道微生物群无法将5-FC主动转化为5-FU。
