Acceleration of the elimination of tenoxicam by cholestyramine in the dog

Two commonly used adsorbents, activated charcoal and cholestyramine, were evaluated in vitro for their ability to adsorb the nonsteroidal anti-inflammatory drug tenoxicam and in vivo for their use in influencing the elimination kinetics of this drug. The Langmuir binding isotherms determined in buffer solutions at pH 7.5 indicated a much greater adsorption capacity of cholestyramine (1.63 g of drug per g of resin) than of charcoal (0.18 g/g of adsorbent) for the acidic drug with a pKa of 5.3. When single i.v. tenoxicam administrations to dogs were followed by multiple p.o. cholestyramine doses the elimination rate of the drug was accelerated drastically. Due to an increased total body clearance (0.65 vs. 0.13 liters/hr), the elimination half-life was reduced from a median base-line value of 31 to 5.4 hr and the mean residence time of drug in the body was decreased from 41 to 7.9 hr. In contrast to cholestyramine, charcoal hardly increased the rate of elimination of tenoxicam over the base-line values determined in the same animals. Inasmuch as these results were similar in all three animals investigated and because the study design precluded an influence of the treatment sequence, it is concluded that cholestyramine efficiently sequesters intestinally secreted tenoxicam and can thereby accelerate drug elimination from the body.