ANTIPYRINE PHARMACOKINETICS IN THE TAIL-SUSPENDED RAT MODEL

As space flight becomes more commonplace, the influence of physiologic changes associated with the microgravity environment become of greate r concern. Exposure to weightlessness has been shown to have numerous effects on body composition and organ function in animals and humans. However, studies examining possible alterations in drug metabolism and pharmacokinetics are not readily available. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of our s tudy was to examine the effects of simulated weightlessness on the pha rmacokinetics of antipyrine. Weightlessness was simulated through the use of the tail-suspended rat model. Rats were suspended for a total o f 7 days. During the study period, antipyrine pharmacokinetics, after a single 20 mg/kg i.v. or p.o. dose, were evaluated at base line (day -1) and 1, 3 and 7 days after the initiation of suspension. Total body clearance was significantly elevated in the tail suspended rats from both the i.v. and p.o. dosing groups after 3 and 7 days of simulated w eightlessness. In addition, clearance was elevated after 1 day of tail -suspension in the p.o. dosing group. Steady-state volume of distribut ion was not statistically different over the entire study period in ei ther dosing group. Data from the present study suggest that brief peri ods of tail-suspension may markedly alter the pharmacokinetics of drug s in the rat and that more studies are required in models of weightles sness and actual space flight to understand the complex interaction be tween microgravity and hepatic metabolic activity.