Effect of citalopram on plasma levels of oral theophylline

Background: Citalopram and theophylline may be prescribed together to treat patients with depression and asthmatic disease. Because theophylline has a low therapeutic index, small changes in plasma levels may result in therap eutic failure or adverse effects. Both citalopram and theophylline are meta bolized by cytochrome P450 (CYP) isozymes. Theophylline is metabolized by C YP1A2; however, the extent to which citalopram interacts with this isozyme in vivo is not known. Objective: This study was conducted to investigate whether citalopram alter s plasma levels of oral theophylline. Methods: Tn an open-label, multiple-dose study, healthy nonsmoking voluntee rs 18 to 45 years of age were administered a single oral dose of theophylli ne (300 mg) on day 1. Beginning on day 3, citalopram 40 mg was administered daily through day 24 to achieve steady-state plasma levels. On day 23 a si ngle oral dose of theophylline 300 mg was coadministered with citalopram 40 mg. Fasting plasma levels of theophylline were measured on day 1 (in the a bsence of citalopram) and on day 23 (in the presence of steady-state plasma concentrations of citalopram) periodically for 36 hours. Results: Thirteen subjects (8 men and 5 women) participated; all completed the study. One subject was not included in the pharmacokinetic calculations . Citalopram treatment had no effect on the pharmacokinetic characteristics of theophylline. Conclusions: Citalopram dosing to steady state did not inhibit or induce th e metabolism of theophylline in this population of healthy volunteers. Dose adjustment of theophylline thus may not be necessary in patients receiving concurrent therapy with citalopram.