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No Pharmacokinetic or Pharmacodynamic Interaction Between Theophylline and the Leukotriene Biosynthesis Inhibitor BAY x 1005
Author(s) -
Groen Henk,
Moesker Harm L.,
Leeuwenkamp Oscar R.,
Sollie Frans A. E.,
Jonkman Jan H. G.
Publication year - 1996
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1996.tb04229.x
Subject(s) - theophylline , pharmacokinetics , cmax , morning , bronchodilator , pharmacology , area under the curve , medicine , tolerability , pharmacodynamics , crossover study , volume of distribution , chemistry , adverse effect , placebo , asthma , alternative medicine , pathology
An open, randomized, three‐period crossover study was conducted to compare the steady‐state pharmacokinetics, pharmacodynamics, and tolerability of concomitant administration of BAY × 1005 and theophylline in 12 healthy volunteers. BAY × 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 × 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 1 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 12‐hour dosing interval (AUC) for treatment C versus B for theophylline on day 7 was 98% for both parameters. For BAY × 1005, the ratios of treatment C versus treatment A were 94% for C max and 101 % for AUC. Plasma LTB 4 remained virtually unchanged during either treatment. Steady‐state concentrations of theophylline were not affected by concomitant BAY × 1005 intake, and addition of theophylline had no clinically relevant effect on steady‐state plasma concentrations of BAY × 1005. The combination of theophylline and BAY × 1005 did not lead to a change in nature, intensity, or frequency of adverse events.