Melzer E, Bardan E, Ronen I, Krepel Z, Bar Meir S
Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel.
Eur J Drug Metab Pharmacokinet. 1994 Apr-Jun;19(2):151-5. doi: 10.1007/BF03188835.
Interferons (IFN) inhibit activity of many isoenzymes of the hepatic microsomal cytochrome P-450 system. This inhibition is species specific. Lidocaine is metabolized by cytochrome P-450 III A 4. We investigated in the rat the effect of rat alpha-IFN on lidocaine elimination and on its extraction by the isolated perfused rat liver. To determine elimination, the femoral artery and vein were cannulated. 24 h later, the conscious rat was given lidocaine through the venous catheter and blood was drawn from the arterial catheter for lidocaine determination every 3 min for 20 min. 7 rats were pre-treated with intramuscular rat alpha-IFN 7.5 x 10(5) U, 24 h prior to the experiment and another 4 rats were given saline i.m. The lidocaine elimination rate constant was unchanged, 0.065 min-1 and 0.063 min-1 for the control and IFN groups, respectively. To investigate lidocaine extraction, the isolated perfused rat liver was used. Perfusate samples from the portal and hepatic veins were drawn at 2 min intervals for 20 min, and lidocaine extraction determined. Extraction was determined in two groups of 6 rats each. The first group served as control and these rats were injected with saline only, while in the second group, the rats were pre-treated with rat alpha-IFN 7.5 x 10(5) U. Lidocaine extraction by the isolated perfused rat liver remained unchanged, 97.0 +/- 0.7% and 94.0 +/- 2.4% in the control and IFN treated groups, respectively. It is concluded that the rat alpha-IFN affects neither the elimination nor the extraction of lidocaine.
干扰素(IFN)可抑制肝微粒体细胞色素P - 450系统的多种同工酶的活性。这种抑制具有种属特异性。利多卡因由细胞色素P - 450 III A 4代谢。我们在大鼠中研究了大鼠α - IFN对利多卡因消除及其被离体灌注大鼠肝脏摄取的影响。为测定消除情况,将股动脉和静脉插管。24小时后,给清醒大鼠经静脉导管注射利多卡因,并在20分钟内每隔3分钟从动脉导管取血测定利多卡因含量。7只大鼠在实验前24小时经肌肉注射大鼠α - IFN 7.5×10⁵ U进行预处理,另外4只大鼠经肌肉注射生理盐水。利多卡因消除速率常数未改变,对照组和干扰素组分别为0.065分钟⁻¹和0.063分钟⁻¹。为研究利多卡因摄取情况,使用离体灌注大鼠肝脏。每隔2分钟从门静脉和肝静脉采集灌注液样本,共采集20分钟,然后测定利多卡因摄取情况。在两组各6只大鼠中进行测定。第一组作为对照,仅给这些大鼠注射生理盐水,而在第二组中,大鼠经大鼠α - IFN 7.5×10⁵ U预处理。离体灌注大鼠肝脏对利多卡因的摄取保持不变,对照组和干扰素处理组分别为97.0±0.7%和94.0±2.4%。结论是大鼠α - IFN既不影响利多卡因的消除,也不影响其摄取。