Pharmacokinetic/pharmacodynamic consequences of space flight.

As astronauts prepare for long-term space missions, the question arises of whether drug medication in a zero gravity environment will have the same effects as under normal gravity. There are two potential kinds of changes that must be evaluated: alterations of pharmacokinetics and pharmacodynamics. Pharmacokinetic changes will affect the drug concentrations produced by a certain dosage regimen. They can be caused by changes in: (1) intrinsic clearance (e.g., enzyme activity and renal function), (2) drug binding (e.g., protein binding and tissue binding), (3) blood flow (e.g., liver blood flow and renal blood flow), and (4) bioavailability (e.g., rate and extent of absorption). Pharmacodynamic changes will affect the response that is produced by a given drug concentration. They can be caused by changes in drug-receptor interaction or changes in disease characteristics. Studies of pharmacokinetic and pharmacodynamic changes in microgravity are limited, and predictions of any alterations are mainly extrapolated from known relationships between certain physiologic parameters and their effects on pharmacokinetics in normal gravity. Almost no data is available on changes in pharmacodynamics. Also, no information is available on the relationship between pharmacokinetics and pharmacodynamics. More studies are needed to elucidate the changes in pharmacokinetics and pharmacodynamics in microgravity to ensure the optimum use of drug therapy during space flight.