Chirstophidis N, Vajda F J, Lucas I, Drummer O, Moon W J, Louis W J
Clin Pharmacokinet. 1978 Jul-Aug;3(4):330-6. doi: 10.2165/00003088-197803040-00006.
The pharmacokinetics of fluorouracil after oral, intravenous and rectal administration were compared in 12 patients with colorectal cancers. Oral administration of 10 to 15 mg/kg gave variable plasma levels (0 to 10.5 microgram/ml) and bioavailability (0 to 74%; mean 28%). Bioavailability increased markedly with increases in dose, suggesting saturation of the 'first pass' hepatic metabolism of the drug. Differences in bioavailability could not be related to standard liver function tests or the presence of metastatic deposits in the liver. Plasma levels were not detectable after rectal administration in the 4 patients studied and were very low (0 to 8 microgram/ml) during high dose (20 to 30 mg/kg/24h) slow intravenous infusion in 6 patients. These findings indicate that different dose schedules and routes of administration produce markedly different plasma levels. They suggest that the rate of degradation of fluorouracil by the liver is quite variable and may become saturated with increasing dose. For these reasons monitoring of plasma levels of the drug in individual patients may be useful.
对12例结直肠癌患者比较了口服、静脉注射和直肠给药后氟尿嘧啶的药代动力学。口服10至15mg/kg时，血浆水平变化较大（0至10.5微克/毫升），生物利用度为0至74%（平均28%）。生物利用度随剂量增加而显著增加，提示该药肝脏“首过”代谢存在饱和现象。生物利用度的差异与标准肝功能检查或肝脏转移灶的存在无关。在4例接受直肠给药研究的患者中，未检测到血浆水平；在6例接受高剂量（20至30mg/kg/24小时）缓慢静脉输注的患者中，血浆水平非常低（0至8微克/毫升）。这些发现表明，不同的给药方案和给药途径会产生明显不同的血浆水平。提示肝脏对氟尿嘧啶的降解速率变化很大，且可能随剂量增加而饱和。基于这些原因，监测个体患者的药物血浆水平可能是有用的。
