Effect of pH on the binding of theophylline to serum proteins.

The binding of theophylline to serum protein within the pH range of 7.0 to 7.8 was determined by equilibrium dialysis using serum from 8 healthy adult volunteers. The percentage of theophylline bound was independent of the total concentration of the drug, but was directly related to pH. Because changes in the free fraction of theophylline may alter the therapeutic response, toxic effects, and pharmacokinetics, any future studies of the pharmacology of theophylline should include assessment of the acid-base status of the patients and measurements of free as well as total theophylline concentrations.