Changes of antipyrine pharmacokinetics during influenza and after administration of interferon-alpha and -beta

During viral infections serum levels of interferons are elevated. In this study we wanted to observe the effects of endogenous interferon (IFN) during an acute viral infection (influenza) and after external application of interferons on the pharmacokinetics of antipyrine which is a parameter of hepatic cytochrome P450 enzyme activity.

Endogenous plasma levels of interferons and the antipyrine pharmacokinetics in 10 otherwise healthy volunteers were investigated before outbreak and in the symptomatic interval of an acute viral respiratory infection. The serum interferon levels were determined by RIA. In another trial 2 groups of 9 HIV patients each in stage CDC/WHO B2/3 received low-dose interferon therapy with 0,75 Mio. I.U. interferon-alpha or -beta s.c./die. The concentrations of antipyrine in serum were measured by HPLC. The antipyrine kinetics were determined before the infection or the interferon therapy, respectively, and during viral infection or during interferon or after interferon therapy, respectively.

The plasma levels of IFNalpha and IFNgamma were significantly elevated from 4.7 U/ml to 12.6 U/ml and 0.3 U/ml to 3.4 U/ml, respectively, whereas the antipyrine clearance showed a decrease from 57.9 ml/min to 45 ml/min in the symptomatic interval of an acute viral infection. During therapy with low-dose interferons we observed a significant difference after 12 week treatment with IFNalpha or IFNbeta, respectively. In the first group we observed a decreased antipyrine clearance from 49.0 ml/min to 41.7 ml/min; in the second group the antipyrine clearance decreased from 49.0 ml/min to 41.7 ml/min.

Viral infections (influenza) are able to inhibit the hepatic monooxygenase system due to elevated serum interferon levels. Low doses of exogenous interferons inhibit the cytochrome P450 monooxygenase system.