The Effect of Whole Virus Influenza Vaccination on Theophylline Pharmacokinetics

Abstract

The effect of whole virus influenza vaccination on theophylline pharmacokinetics was evaluated in 16 normal subjects. Because previous reports had suggested that influenza vaccine induces interferon production and may potentially depress hepatic metabolism of theophylline, serum interferon concentrations were monitored for 6 days after vaccination. Lymphocytes from 6 subjects were incubated in vitro with dilute whole virus vaccine (WVV) or dilute split virus vaccine (SVV) to assess their immunocompetence and the immunogenic potential of the 2 vaccine preparations. Additionally, influenza antibody response was monitored by prevaccination and postvaccination serum antibody titers in 11 subjects. No significant change in half-life, total body clearance, volume of distribution of maximal serum theophylline concentration compared to prevaccine values was observed at either 2 or 6 days after vaccination. No interferon production was detected in vivo up to 6 days after vaccination. In vitro lymphocyte interferon induction assay demonstrated mean interferon levels of 12,252 +/- 9,819 IU/ml for WVV and 888 +/- 1,180 IU/ml for SVV (p less than 0.05), demonstrating the immunocompetence of the subject's lymphocytes and confirming the greater immunogenic potential of WVV. Seven of 11 subjects (64%) showed a 4-fold rise in influenza antibody titer to at least one of the vaccine antigens. We conclude that whole virus influenza vaccine does not alter theophylline pharmacokinetics. In addition, it has greater immunogenic potential than split virus vaccine in vitro but does not induce significant interferon production in vivo. This study adds further evidence supporting the safety of the concomitant use of influenza vaccine in patients taking theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)