Effects of influenza virus vaccine on hepatic drug metabolism

Abstract

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 alpha-interferon levels rose after vaccination for only about 8 hours, and levels of gamma-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.

Influence of Tetanus and Typhoid Vaccines on Hepatic Drug Metabolism

“…NS = 0.05; **p < 0.01 vs. controls. Not significant; * p < tive of an inhibition of liver drug-metaboliz ing enzymes induced by tetanus vaccine [Chambers and Jefferson, 1982;André et al, 1984], Interestingly, the transient inhibitory influence of tetanus vaccine is consonant with previous investigations: Meredith et al [1985] noted a decreased rate of theophylline oxidation 1 day but not 7 days after in fluenza vaccination.…”

“…For instance, vaccination with bacil lus Calmctte-Guérin was found to impair theophylline elimination in humans [Gray et al, 1983] whereas BordeteUa pertussis vac cine decreased phenytoin hydroxylation and elimination rate in rats [Renton, 1979], In contrast, hepatitis B vaccine failed to impair antipyrine clearance in humans [Bachmann et al, 1985]. The effect of influenza vaccine has been more extensively investigated but remains equivocal: increased theophylline or phenytoin serum levels [Renton et al, 1980;Walker et al, 1981;Goldstein et al, 1982;Levine et al, 1984;Meredith et al, 1985], enhanced anticoagulant response [Kramer et al, 1984] and depression of antipyrine and aminopyrine metabolism [Kramer and McClain, 1981;Simonet et al, 1986] have been reported in humans following influenza vaccination, although negative results were also noted [Fischer et al, 1982;Patriarca et al, 1983;Stults et al, 1983;Bukowskyj et al, 1984;Lipsky et al, 1984].…”

Effect of influenza vaccination on serum clozapine and its main metabolite concentrations in patients with schizophrenia

“…Some case reports have suggested that in¯uenza vaccination depresses the theophylline metabolism in humans implying an inhibitory eect on CYP1A2 enzyme, which is the enzyme mainly responsible for theophylline metabolism [6,7,20]. Some other studies found no eect of in¯uenza vaccination on theophylline pharmacokinetics [21,22].…”

“…In some case reports, the pharmacokinetics of another CYP1A2 substrate, theophylline, was altered by in¯uenza vaccination leading to elevated serum theophylline concentrations [6,7]. However, the eects of in¯uenza vaccination on the pharmacokinetics of clozapine are not known.…”

Immune system - drug metabolism interactions: Toxicological insight

“…In humans CYP2A6, CYP2A7, CYP2C19 and CYP3A4 (52) were down-regulated in HBV-and/or HCV-infected livers compared with normal livers. In uenza virus vaccination down regulate CYP 1A2 expression (29). In human immunode ciency virus-positive patients CYP 2D6 expression was also decreased (53).Some liver enzyme activities as CYP 2E1 and CYP 4A, alcohol dehydrogenase and N-acetyltransferase were even found to be increased (54) and some subfamily (CYP 2B and 3A) to be decreased (55) in AA or LPS treated rats.…”