O'Malley K, Stevenson I H, West M
Pharmacology. 1975;13(1):12-9. doi: 10.1159/000136880.
The effect of fenfluramine, administered orally in a daily dose of 1 mg/kg for 40 days, on the disposition and rate of elimination of antipyrine was studied in 15 obese patients. Although the plasma half-life of antipyrine was unchanged, the apparent volume of distribution (1/kg) fell by 11.6% (p less than 0.001) and the plasma metabolic clearance rate (1/kg/h) of antipyrine was reduced by 14.1% (p less than 0.01). No correlation occurred between change in clearance, on the one hand, and change in patient weight or apparent volume of distribution of antipyrine, on the other. In vitro drug-metabolizing enzyme activity in the rat was measured using rate of aminopyrine and hexobarbital metabolism as indices. Fenfluramine inhibited the metabolism of both substrates. It is concluded that fenfluramine can diminish the rate of elimination of drugs which are extensively metabolized by reduction of microsomal enzyme activity. Also, drug clearance may be diminished by reduction of apparent volume of distribution.
在15名肥胖患者中研究了口服苯氟拉明（每日剂量1mg/kg，持续40天）对安替比林处置和消除速率的影响。尽管安替比林的血浆半衰期未改变，但安替比林的表观分布容积（L/kg）下降了11.6%（p<0.001），其血浆代谢清除率（L/kg/h）降低了14.1%（p<0.01）。一方面清除率的变化与另一方面患者体重的变化或安替比林表观分布容积的变化之间无相关性。以氨基比林和己巴比妥的代谢速率为指标测定大鼠体外药物代谢酶活性。苯氟拉明抑制两种底物的代谢。结论是苯氟拉明可通过降低微粒体酶活性来减少经广泛代谢的药物的消除速率。此外，药物清除率可能因表观分布容积的减少而降低。
