Effects of influenza virus vaccine on hepatic drug metabolism

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Abstract
Experimental and more limited clinical studies 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. The effects of influenza vaccine on the metabolism of 3 commonly used drugs: chlordiazepoxide, theophylline, and lorazepam was studied. Healthy male subjects were studied just before and 1 and 7 days after vaccination. Lorazepam metabolism, which proceeds by glucuronidation and not oxidation, was not altered by vaccination. The oxidation of chlordiazepoxide was not depressed by the vaccine. Theophylline oxidation, which proceeds primarly by microsomal oxidation (demethylation), was significantly decreased 1 day, but not 7 days, after vaccination. Serum .alpha.-interferon levels rose after vaccination for only about 8 h, and levels of .gamma.-interferon rose to about 500 IU/ml at 24 h, peaked at 72 h, and returned to normal by 100 h after dosing. The higher the theophylline clearance before vaccination, the greater the degree of clearance depression after vaccination. 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.