Theophylline serum protein binding in obstructive airways disease

The percentage of theophylline bound to protein in sera obtained from patients with obstructive airways disease was determined by ultrafiltration. The bound theophylline fraction in 71 serum specimens collected from 51 patients was 60.7 ± 10.0% ( x ± SD) and ranged from 30.8% to 83.2%. The correlation between unbound serum theophylline concentration and total concentration (range 0.8 to 90 mg/l) was linear (r = 0.97, p < 0.001). Theophylline binding correlated poorly with serum albumin (r = 0.39) and total serum protein (r = 0.35), although the correlations were statistically significant (p < 0.05). Theophylline binding in women did not differ from that in men. The extent of theophylline binding in younger patients was greater than in patients over 55 yr (64.3 ± 8.5% and 57.0 ± 10.4%, p < 0.005). Variation in theophylline binding in 12 patients from whom two or more serum samples were collected was relatively small. Analysis of variance showed interpatient variation in theophylline binding (p < 0.01) but not between sampling occasions in the same patient. The demonstrated variability in serum protein binding of theophylline should influence theophylline distribution and elimination kinetics and may be another determinant of clinical response. Patients with lower binding levels should have higher plasma levels of unbound drug after a loading dose and will need more frequent dosing. Clinical Pharmacology and Therapeutics (1981) 29 , 776–781; doi: 10.1038/clpt.1981.110