Pharmacology in space: pharmacokinetics.
The possible pharmacokinetic mechanisms affected by microgravity are listed in Table 5. In studies of pharmacokinetics in humans, one has generally only access to drug concentrations in plasma and urine which are the results of several concurrent mechanisms. During weightlessness, different changes may occur in each step of the drug disposition process. The most important changes need to be identified and then predicted for the main drugs used in space. The use of a drug as a probe (Table 6) will permit to estimate the changes in specific pharmacokinetic parameters during spaceflight. However, this type of studies is technically difficult to carry out in space, but simulation studies on the ground are easier to perform. Two studies of hepatic blood flow showed no changes in this parameter during bedrest, but a more recent study showed changes in lidocaine disposition during a four-day head-down-tilt. Due to the large differences between individuals, pharmacokinetic changes must be fairly large (> 10-20%) to be observed in studies with probes. To detect a small change in weightlessness will require a number of subjects far higher than can be achieved in spaceflight. In summary, spaceflight is known to change many physiological parameters. The pharmacokinetics of drug disposition is determined by the combination of several complex phenomena. Each step of this process may be influenced by physiopathological changes occurring in spaceflight. This review shows how from a theoretical point of view absorption, distribution and elimination of drugs may be affected by weightlessness. The physiological changes most frequently involved in these modifications are the changes in blood flow due to the fluid shift.
Saivin
S
S
Laboratoire de Pharmacocinétique et Toxicologie Clinique, Hopital Purpan, Toulouse, France.
Pavy-Le Traon
A
A
Soulez-LaRivière
C
C
Güell
A
A
Houin
G
G
D001682:Biological Availability; D004358:Drug Therapy; D064420:Drug-Related Side Effects and Adverse Reactions; D015444:Exercise; D006801:Humans; D007408:Intestinal Absorption; D008657:Metabolic Clearance Rate; D010599:Pharmacokinetics; D011485:Protein Binding; D013026:Space Flight; D014018:Tissue Distribution; D014893:Weightlessness / Q000009:adverse effects*