No pharmacokinetic or pharmacodynamic interaction between theophylline and the leukotriene biosynthesis inhibitor BAY x 1005

An open, randomized, three-period crossover study was conducted to compare the steady-state pharmacokinetics, pharmacodynamics, and tolerability of concomitant administration of BAY x 1005 and theophylline in 12 healthy volunteers. BAY x 1005 (250 mg twice daily; treatment A) and theophylline (400 mg twice daily; treatment B), were administered alone and concomitantly (treatment C) for 6 days with a final morning dose on day 7. The treatments were separated by washout periods of at least 5 days, Pharmacokinetic parameters were derived from concentrations of BAY x 1005 and theophylline as measured by high-performance liquid chromatography in plasma collected before the morning dose on days 5 and 6 and at various times on day 7 of each period until 24 hours after drug administration, Adverse events, vital signs, electrocardiograms, and clinical laboratory studies were monitored as safety parameters. Levels of leukotriene B-4 (LTB(4)) were assessed in plasma collected on days 2 and 7. The treatments were well tolerated by all participants. The ratios of maximum concentration (C-max) and area under the concentration-time curve for one la-hour dosing interval (AUC(t)) for treatment C versus B for theophylline on day 7 was 98% for both parameters, For BAY x 1005, the ratios of treatment C versus treatment A were 94% for C-max and 101% for AUC(t). Plasma LTB(4) remained virtually unchanged during either treatment. Steady-state concentrations of theophylline were not affected by concomitant BAY x 1005 intake, and addition of theophylline had no clinically relevant effect on steady-state plasma concentrations of BAY x 1005. The combination of theophylline and BAY x 1005 did not lead to a change in nature, intensity, or frequency of adverse events.