APPLICATION OF PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODELS FOR ASSESSING DRUG DISPOSITION IN-SPACE

Exposure to weightlessness induces physiologic changes that may lead t o pharmacokinetic and pharmacodynamic alterations of drugs administere d to crew members in flight. Preliminary data from flight and ground-b ased studies indicate that pharmacologically significant changes occur in the kinetics of medications given in weightlessness and in simulat ed microgravity (head-down bed rest). Conducting flight studies on all available medications to identify the changes in their pharmacokineti c behavior in weightlessness is not feasible. An alternative approach for obtaining such information is to use computer simulations employin g physiologically based pharmacokinetic (PBPK) models. Information thu s obtained would be helpful in predicting the therapeutic effectivenes s of medications in space, and also in developing plans for flight stu dies. This paper presents a brief review of relevant physiologic facto rs and pharmacokinetic implications of space flight, and includes a pr eliminary PBPK model for estimating plasma concentration-time profiles of acetaminophen under different experimental conditions.