Pharmacokinetics of theophylline in hepatic disease

The disposition of theophylline was examined in eight male cirrhotic (six proven by biopsy) patients without heart failure. An oral dose of 100 mg of theophylline per square meter of surface area was administered, and samples of serum and saliva were collected from 0 to 60 hours and were assayed by high-pressure liquid chromatographic techniques. Controls were 57 young normal subjects and 25 age-matched patients. The body clearance of theophylline in cirrhotic patients was low, averaging 18.8 ± 11.3 ml/kg/hr (± SD) vs 53.7 ± 19.3 and 63.0 ± 28.5 ml/kg/hr in the control patients and the normal subjects, respectively. The half-life of theophylline in cirrhotic patients was prolonged, with a mean of 28.8 ± 14.3 hours compared to 6.0 ± 2.1 hours in normal subjects. Patients with cirrhosis proven by biopsy had significantly lower values for body clearance and longer half-lives than subjects without biopsies. The values for body clearance correlated well with the serum level of bilirubin (r = -0.84) and the serum level of bile acids (r = -0.81). The slow and variable metabolism in cirrhotic patients necessitates a reduction in the maintenance dosage of aminophylline to 0.20 to 0.45 mg/kg/hr and monitoring of the serum level during therapy.