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 com pare the steady-state pharmacokinetics, pharmacodynamics, and tolerabi lity of concomitant administration of BAY x 1005 and theophylline in 1 2 healthy volunteers. BAY x 1005 (250 mg twice daily; treatment A) and theophylline (400 mg twice daily; treatment B), were administered alo ne and concomitantly (treatment C) for 6 days with a final morning dos e on day 7. The treatments were separated by washout periods of at lea st 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 afte r 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 participant s. The ratios of maximum concentration (C-max) and area under the conc entration-time curve for one la-hour dosing interval (AUC(t)) for trea tment 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 unch anged during either treatment. Steady-state concentrations of theophyl line were not affected by concomitant BAY x 1005 intake, and addition of theophylline had no clinically relevant effect on steady-state plas ma concentrations of BAY x 1005. The combination of theophylline and B AY x 1005 did not lead to a change in nature, intensity, or frequency of adverse events.