Free and total plasma theophylline concentrations in chronic airflow obstruction

It has been suggested that the variability in clinical response between individuals at any given total plasma theophylline concentration may be related to interpatient variability in theophylline plasma protein binding. We therefore measured the plasma protein binding of theophylline in plasma from 39 outpatients with chronic airflow obstruction who were receiving long term oral theophylline treatment. The protein binding was measured at 37 degrees C and pH 7.4 by equilibrium dialysis. Total plasma theophylline concentration was measured by high performance liquid chromatography and the free concentration calculated by multiplying total concentration by the free (unbound) fraction. The total plasma theophylline concentration varied from 0.7 to 22.0 micrograms/ml, mean 10.6 (SD 5.3) micrograms/ml (3.9-121 mumol/l, mean 58.3 (29.2) mumol/l). The free fraction of theophylline varied only from 0.58 to 0.69 (mean 0.626 (0.024] microgram/ml and was not related to the total concentration (r = -0.236, n = 39, p greater than 0.05). There was a very close relationship between free and total plasma concentrations (r = 0.996, n = 39, p less than 0.001). It is concluded that there is little variability in plasma protein binding of theophylline in patients with chronic airflow obstruction. Other factors appear to be responsible for variability between individuals in the response to a given total plasma theophylline concentration.