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The influence of caffeine on the steady-state pharmacokinetics of theophylline
Ist Teil von
Clinical pharmacology and therapeutics, 1991-03, Vol.49 (3), p.248-255
Ort / Verlag
New York, NY: Nature Publishing
Erscheinungsjahr
1991
Link zum Volltext
Beschreibungen/Notizen
During this open, two‐period crossover study in eight healthy volunteers, 1200 mg anhydrous theophylline was administered as a two‐stage infusion during 24 hours on day 6. During one of the 8‐day periods, 300 mg caffeine, t.i.d., was administered orally. After the start of the theophylline infusion, plasma concentrations of theophylline and caffeine and urinary excretion of theophylline and four metabolites were determined frequently during 60 hours. With caffeine administration theophylline steady‐state concentration and area under the curve increased by 23% and 40%, respectively, whereas the volume of distribution at steady state seemed unchanged. The cumulative urinary excretion of 1‐methyluric acid and 1‐methylxanthine did not reach a plateau, suggesting a capacity‐limiting factor in their formation. Notwithstanding the mutual interference of theophylline and caffeine metabolism, the reduction in apparent total body clearance and elimination rate constant of theophylline by 29% and 31%, respectively, indicated a pronounced influence of concomitant administration of realistic amounts of caffeine.
Clinical Pharmacology and Therapeutics (1991) 49, 248–255; doi:10.1038/clpt.1991.24