Conversion from intravenous to oral dosing using sustained-release theophylline tablets

Theophylline total body clearance was determined in asthmatic patients, from steady-state serum theophylline concentrations, measured during a constant-rate, intravenous aminophylline infusion. Theo-Dur dosing rates were calculated from the product of theophylline total body clearance and the desired steady-state theophylline concentration. After stopping the aminophylline infusion, oral doses of Theo-Dur were given every 12 hours. Blood samples were obtained 1, 3, 6,9, and 12 hours after the first oral dose and 12 hours after the second oral dose. Patients were evaluated for compliance and theophylline toxicity after receiving Theo-Dur for one week. Total body clearances and theophylline dosing rates varied more than threefold. The difference between the intravenous steady-state serum concentration and the average oral serum concentration was 1.2 micrograms/ml in patients with similar oral and intravenous dosing rates. The difference between peak and trough serum theophylline concentrations after the first oral dose averaged 7.8 micrograms/ml. Eight of nine patients evaluated after leaving the hospital were compliant, as determined from a tablet count during a clinic visit. Serum theophylline concentrations, determined 12 hours after the last Theo-Dur dose, averaged 10.4 micrograms/ml for the compliant patients.