Variability of the serum protein binding of theophylline in patients with asthma and cystic fibrosis.

Abstract

1. The serum protein binding of theophylline was studied in 28 asthmatics and 11 patients with cystic fibrosis (CF) who were receiving the drug regularly. Peak theophylline samples were collected at 2 week intervals on four occasions in each asthmatic and on three occasions in each CF patient. The binding was measured using ultrafiltration at 37 degrees C and pH 7.4. The total and free (unbound) theophylline concentrations were measured using high‐performance liquid chromatography. 2. The mean free‐fractions (+/‐ s.d.) in asthmatics (0.50 +/‐ 0.03) and in CF patients (0.51 +/‐ 0.04) were not significantly different. The intra‐ and inter‐subject variability in the free‐fraction (fu) was relatively small in both patient groups. The binding was found to be concentration‐independent at serum theophylline concentrations up to 30.9 micrograms ml‐1. The effects of age, gender, serum albumin and total serum protein on the free fraction were evaluated. 3. The results indicate that the binding of theophylline is similar in the two disease states. The low degree of variability in serum theophylline binding indicates that measurements of total serum theophylline concentrations will reflect unbound serum concentrations with acceptable accuracy in both patient groups studied. 1992 The British Pharmacological Society