[Effects of plasma albumin on theophylline concentration in lung tissue]

To study the relationship between plasma and lung tissue theophylline concentrations, we changed the number of binding sites for theophylline on serum albumin. Cefazoline, which competes with theophylline for those binding sites, was given to rats, and free theophylline was separated by ultrafiltration. The dose of cefazoline was directly related to the percentage of free theophylline and was inversely related to the plasma total theophylline concentration. The plasma free theophylline concentration, however, was unchanged at the lower doses of cefazoline and was low only at the highest dose. The concentration of theophylline in lung tissue was inversely related to the dose of cefazoline. The concentration of 1, 3-dimethyluric acid, a major metabolite of theophylline, was also inversely related to the dose of cefazoline, which suggests that the metabolic rate of theophylline did not increase. Excretion of theophylline via the urine might be accelerated by its diuretic action. We conclude that when the binding of theophylline to plasma proteins is altered in rats, the concentration of free theophylline in plasma does not reflect the concentration of theophylline in lung tissue. Instead, the total theophylline concentration in plasma can be used as an index of the concentration in lung tissue.