THE DISPOSITION OF THEOPHYLLINE IN PATIENTS WITH LUNG AND BREAST-CANCER

The influence of extrahepatic neoplastic disease on the biotransformat ion of theophylline was assessed by comparing the pharmacokinetic and metabolic profile of the drug in six patients with advanced breast or bronchial carcinoma, without detectable liver metastases, and in six a ppropriately matched control subjects. Each subject was given a single dose of theophylline (5 mg/kg) in oral solution; blood and urinary sa mples were collected for up to 24h after dosing. Theophylline was abso rbed rapidly in ail subjects and within 2h reached comparable peak con centrations in both groups (cancer patients: 57.8 +/- 14.4 mu mol/l; c ontrols, 65.0 +/- 10.6 mu mol/l; N.S., means +/- s.d.). No significant differences were observed between cancer patients and controls for th eophylline apparent volume of distribution (0.44 +/- 0.07 vs 0.40 +/- 0.06l/kg), total body clearance (40.8 +/- 12.8 vs 34.8 +/- 13.0mlkg(-1 ) h(-1)) and elimination half-life (8.0 +/- 1.6 vs 8.5 +/- 1.8 h). The excretion of the major metabolites 3-methyl-xanthine and 1,3-dimethyl -uric acid was also very similar in the two groups. These data do not provide any evidence for an altered rate or pattern of theophylline bi otransformation in patients with advanced extrahepatic neoplastic dise ase.