Endogenous interferon plasma levels and antipyrine pharmacokinetics in patients with viral infections

Abstract

We investigated the pharmacokinetics of antipyrine and the endogenous plasma levels of interferon alpha (IFN alpha), interferon beta (IFN beta) and interferon gamma (IFN gamma) in 10 otherwise healthy volunteers before outbreak (baseline) and in the symptomatic interval of an acute viral respiratory infection, and also in HIV-1 infected homosexual patients in stadium WR 2-3 (n = 11) and WR 5-6 (n = 11) before and one day after application of the antiretroviral agent zidovudine 800 mg day-1 for 14 days. Interferons were measured by RIA or ELISA, respectively. The concentrations of antipyrine and its metabolites in serum and urine were measured by HPLC. Antipyrine is a pharmacokinetic model substance to estimate the cytochrome P 450 enzyme activity. The plasma levels of IFN alpha and IFN gamma in the symptomatic interval of an acute viral respiratory infection were elevated from 4.7 U ml-1 to 12.6 U ml-1 and from 0.3 U ml-1 to 3.4 U ml-1, respectively. The antipyrine clearance showed a significant decrease from 57.9 ml min-1 to 45.0 ml min-1. In the HIV-1 infected patients in stadium WR 2-3 no alterations in plasma levels of interferons or in the pharmacokinetics of antipyrine were observed after treatment with zidovudine. In contrast to these results, in patients in stadium WR 5-6 we found a significant decrease of IFN alpha and an elevation of the clearance and the clearances to metabolite of antipyrine by about 20 percent.