Clinical evaluation of theophylline binding to plasma protein in bronchial asthmatic patients.

Theophylline binding to plasma protein was studied with seven bronchial asthmatic inpatients. The extent of protein binding was monitored using an ultrafiltration device, EMIT FreeLevelTM System 1, whose performance is pH independent between 7.5 and 8.5 and concentration independent between 2 and 10 mcg/ml. When protein-free theophylline solutions are used a linear pH dependency was observed between 7.0 and 8.3. With theophylline-spiked human plasma using the same samples, the binding was found to be concentration-independent in the range 5 to 40 mcg/ml. The intra- and inter-individual variations in theophylline binding to plasma proteins were relatively large. A calculation procedure for predicting free fractions at normal physiological plasma pH, 7.4, using the observed free fraction at a given plasma pH is proposed. A good correlation was obtained between plasma and salivary theophylline concentrations. Salivary levels alone, however, are unreliable for monitoring theophylline therapy.