Modulation of antipyrine and theophylline pharmacokinetics by adequate and excessive dietary protein in F344 male rats

Abstract The pharmacokinetics of antipyrine and theophylline were evaluated in male F344 weanling rats relative to consumption of nutritionally adequate (12%) versus excessive (22% as found in commonly available commercial laboratory diets) levels of dietary protein. Plasma half-lives were reduced significantly for both compounds with an increase from 12 to 22% dietary protein. The volume of distribution of theophylline was not altered by variation in protein consumption, however the volume of distribution of antipyrine was significantly elevated in animals consuming nutritionally adequate (12%) versus excessive (22%) levels of dietary protein. The clearance rate for both compounds was significantly elevated with an increase from 12 to 22% protein. The magnitude of differences in the plasma half-life between the two dietary groups was greatest for theophylline. These data lend support to the suggested replacement of the commonly used laboratory feeds (22% dietary protein which are designed for optimal growth rate) with a diet that provides a nutritionally adequate (12%) quantity of dietary protein. Furthermore, these data, in conjunction with our earlier reports (2,3) underscore the need for including dietary regimen when interpreting and publishing the results of experiments conducted on Laboratory Animals.