Effects of influenza virus vaccine on hepatic drug metabolism
Effects of influenza virus vaccine on hepatic drug metabolism
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流感病毒疫苗对肝脏药物代谢的影响
DOI：
10.1038/clpt.1985.61
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发表时间：
1985
影响因子：
6.7
通讯作者：
S. Schenker
中科院分区：
文献类型：
--
作者：
C. Meredith;Charles D Christian;Raymond F. Johnson;Rebecca Troxell;G. Davis;S. Schenker
实验和更有限的临床研究表明，流感疫苗接种可能会抑制各种药物的氧化肝脏代谢，并导致药物毒性。所谓的机制是干扰素的形成和由此导致的可用于药物氧化的细胞色素P-450的减少。由于这些报告的临床和基础科学的影响，我们承诺研究流感疫苗对三种常用药物代谢的影响：利血平，茶碱和劳拉西泮。我们的健康男性受试者在疫苗接种前、接种后1天和7天进行了研究。正如预期的那样，劳拉西泮代谢（通过葡萄糖醛酸化而非氧化进行）未被疫苗接种改变。然而，令人惊讶的是，利血平的氧化也没有被疫苗抑制。茶碱氧化，这主要是通过微粒体氧化（去甲基化），是显着减少1天，但不是7天后，接种疫苗。血清α干扰素水平在接种后仅上升约8小时，γ干扰素水平在24小时上升至约500 IU/ml，在72小时达到峰值，并在给药后100小时恢复正常。似乎接种前茶碱清除率越高，接种后清除率下降的程度越大。因此，流感疫苗接种后药物氧化的抑制是选择性的，每种药物都应该单独研究。茶碱清除率下降的程度很小且短暂，在接种前清除率较高的受试者中似乎更大。
Experimental and more limited clinical studies have suggested that influenza vaccination may depress the oxidative hepatic metabolism of various drugs and lead to drug toxicity. The alleged mechanism is the formation of interferon and the resulting decrease in cytochrome P‐450 available for drug oxidation. Because of the clinical and basic science implications of these reports, we undertook to study the effects of influenza vaccine on the metabolism of three commonly used drugs: chlordiazepoxide, theophylline, and lorazepam. Our healthy male subjects were studied just before and 1 and 7 days after vaccination. As expected, lorazepam metabolism, which proceeds by glucuronidation and not oxidation, was not altered by vaccination. Surprisingly, however, the oxidation of chlordiazepoxide was also not depressed by the vaccine. Theophylline oxidation, which proceeds primarily by microsomal oxidation (demethylation), was significantly decreased 1 day, but not 7 days, after vaccination. Serum α‐interferon levels rose after vaccination for only about 8 hours, and levels of γ‐interferon rose to about 500 IU/ml at 24 hours, peaked at 72 hours, and returned to normal by 100 hours after dosing. It appeared that the higher the theophylline clearance before vaccination, the greater the degree of clearance depression after vaccination. Thus the inhibition of drug oxidation after influenza vaccination is selective and each drug should be studied individually. The degree of depression of theophylline clearance is small and transient and appears to be greater in subjects with higher prevaccination clearance.
小棒状杆菌治疗后大鼠肝脏药物代谢的抑制。
影响因子：
5.8
作者：
Farquhar,D;Benvenuto,JA;Kuttesch,N;Loo,TL
通讯作者：
Loo,TL