Dose-dependency in the Exsorption of Theophylline and the Intestinal Dialysis of Theophylline by Oral Activated Charcoal in Rats

Abstract

The elimination half-life of theophylline in serum after intravenous (i.v.) administration of aminophylline increased with increase in dose. Exsorption of theophylline from blood to the gastrointestinal tract was investigated after i.v. administration of aminophylline (10–50 mg kg−1) to rats by the in-situ single-pass perfusion technique. The exsorption rate of theophylline into the intestinal lumen also increased with increase in dose. When the dose of aminophylline was increased five-fold from 10 to 50 mg kg−1, the amount of theophylline exsorbed in 120 min was proportionally increased from 450 to 2300 μ g. The average extent of theophylline exsorbed into the intestinal lumen was 12–15% after doses from 10–50 mg kg−1, while the extent of the drug excreted into the bile varied from 0.17–0.30% after doses from 10–50 mg kg−1. However, intestinal and biliary clearance of theophylline did not change significantly in the range 10 to 50 mg kg−1. Oral administration of multiple doses of activated charcoal reduced the serum theophylline levels after i.v. administration of aminophylline (50 mg kg−1) to rats. The serum half-life and the area under the serum concentration-time curve of theophylline were decreased to 52 and 50% by the charcoal treatment, respectively, while the total body clearance of the drug was increased to 188% compared with the corresponding control experiments. The volume of distribution was not significantly different between treated and control rats. As the total body clearance after a high dose is less than after a low dose, because there is a decreased endogenous clearance (as observed in theophylline overdose), clearance after a high dose may be more enhanced by oral activated charcoal than that after a low dose.