Fig. 4

Pharmacokinetic and pharmacodynamic spaceflight and analog studies. Flown human studies, flown rodent studies, bedrest human analog studies, and hind-limb suspension rodent analog studies of PK/PD alterations in spaceflight. Drugs studied, publication dates, and duration (where available) are provided. Medications highlighted in red demonstrated significant alteration of PK/PD during spaceflight^36,37,39,40 (or analog^{48,49,50,51,52,53,54,55,56,57}). Medications highlighted in blue were anecdotally reported to be less effective during spaceflight compared to before or after spaceflight (percent of doses reported to be less effective is highlighted).^5,6 Rodent studies of enzyme production or metabolism are similarly indicated. Enzymes highlighted in red demonstrated alteration in production or activity during flight^{25,26,41,42,43,44,45,46} (or analog^55,61,62,63) compared with ground controls. Two validation studies were performed (gray lines) between flown rats and hind-limb suspension models,^24,47 both suggesting poor correlation between spaceflight and the hind-limb suspension model. To date, there have been neither validation studies of the human bedrest model to human spaceflight PK/PD response nor have there been any validation studies comparing flown animal response to that of flown humans. cGMP cyclic guanosine monophosphate