Echizen H, Ohta Y, Shirataki H, Tsukamoto K, Umeda N, Oda T, Ishizaki T
Division of Geriatric Health and Nutrition, National Institute of Nutrition, Tokyo, Japan.
J Clin Pharmacol. 1990 Jun;30(6):562-7. doi: 10.1002/j.1552-4604.1990.tb03621.x.
To determine whether natural human interferon administered under the usual therapeutic dosing scheme would inhibit the hepatic drug metabolism, we performed an antipyrine test in eight patients with chronic B or non-A, non-B hepatitis before and after a subchronic interferon therapy (6 megaunits/day for 17 +/- 4 days, mean +/- SD). Six patients received interferon-beta and 2 received interferon-alpha. To circumvent a possible influence of interferon-induced fever on the hepatic drug metabolism, the antipyrine test during the interferon therapy was performed at least 14 days after the interferon-induced fever disappeared. The kinetic parameters of antipyrine were obtained from seven saliva samples over 32 hours postdose. There were no significant differences in any kinetic parameters of antipyrine observed before and during the interferon therapy. With the sample size of the study, there was only a 20% chance (i.e., beta-power = 0.8 at alpha = 0.05) that we might have missed a 17% reduction in antipyrine clearance by the interferon therapy (type II error). On the other hand, the subchronic interferon therapy lowered serum aminotransferases and DNA polymerase activity significantly (P less than .05) compared with the respective baseline values. Our results suggest that the subchronic therapeutic dosing scheme of interferon as conducted in the present study does not cause the inhibitory effect on the oxidative drug metabolism to a statistically significant or clinically relevant degree in patients with chronic hepatitis, while it improves their liver function. Further studies are required for determining if different types of interferons administered under the different dosing schemes would alter the hepatic drug metabolism and the inhibitory effect would be time-dependent.
为了确定按照常规治疗剂量方案给予天然人干扰素是否会抑制肝脏药物代谢，我们对8例慢性乙型或非甲非乙型肝炎患者在亚慢性干扰素治疗（6百万单位/天，持续17±4天，均值±标准差）前后进行了安替比林试验。6例患者接受β干扰素，2例接受α干扰素。为了避免干扰素引起的发热对肝脏药物代谢产生可能的影响，在干扰素治疗期间的安替比林试验在干扰素引起的发热消失至少14天后进行。在给药后32小时内从7份唾液样本中获取安替比林的动力学参数。在干扰素治疗前和治疗期间观察到的安替比林的任何动力学参数均无显著差异。根据该研究的样本量，我们可能漏过干扰素治疗使安替比林清除率降低17%的情况（Ⅱ类错误）的概率仅为20%（即，在α = 0.05时β效能 = 0.8）。另一方面，与各自的基线值相比，亚慢性干扰素治疗显著降低了血清转氨酶和DNA聚合酶活性（P < 0.05）。我们的结果表明，本研究中进行的亚慢性干扰素治疗方案在慢性肝炎患者中不会对氧化药物代谢产生统计学上显著或临床相关程度的抑制作用，同时它改善了患者的肝功能。需要进一步研究以确定在不同给药方案下给予不同类型的干扰素是否会改变肝脏药物代谢以及抑制作用是否会随时间变化。
