0509. Effects of altitude on pharmacokinetics and pharmacodynamics

Substantial numbers of South Africans live at relatively high altitude (HA) or move frequently between sea level and HA. The exposure to HA produces several physiological changes that may affect drug kinetics and consequently also drug actions. Studies have indicated that drugs that are highly bound to plasma proteins are most likely to be affected, but drugs that bind to red cells and/or are metabolized by red cells will also be affected. Prednisolone, for example, is highly bound to plasma proteins but poorly bound to red cells. Results in volunteers studied at altitude compared to sea level (SL) have shown that binding increased significantly at HA vs SL (with higher binding after chronic HA than with acute exposure) and volume of distribution and clearance diminished. Furosemide has also been studied and shown to be affected by HA, but differently from prednisolone in that protein binding decreased and concentrations in plasma water increased (i.e. the free fraction increased). In those studies other interesting changes included an increase in bilirubin levels as total proteins increased with HA. Altitude has also been shown to increase either metabolism or elimination of caffeine, clearance of lithium and also of acetozolamide (obviously important because the latter is actually used to treat altitude sickness). Clinical data are lacking (i.e. the impact of these changes on patients) but it is certainly worth noting that changes might occur in chronic drug users who move between the coast and HA.

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