Pharmacokinetics of lithium in healthy volunteers after exposure to high altitude

Abstract

Introduction: Exposure of the human body to high altitude causes a number of physiological changes. In previous studies, we observed that these changes may alter the pharmacokinetics of drugs. The number of erythrocytes/mm3 increases both, after acute exposure to high altitude (HA), i.e. within 12 - 24 h after reaching high altitude (H), as well as in chronic exposure (HC) (> 10 months) to H. Also binding of drugs to biologic material may change with exposure to HA and/or HC.

Objective: Since lithium is transported into and out of erythrocytes and binds strongly to erythrocytes, but is not plasma protein-bound, we selected this drug as candidate for the present study.

Subjects, material and methods: Lithium carbonate 300 mg were administered orally to young healthy volunteers. One group residing at low altitude (Santiago, Chile, 600 m, group L), these same volunteers after 15 hours of exposure to high altitude (4,360 m, group HA), and volunteers living at high altitude for at least 10 months (group HC).

Results: We found a significant increase of both hematocrit and red blood cell count (RBC) after exposure to H, both, acute or chronic. Elimination half-life increased 64.1% in group HA and 111.4% in group HC in comparison to group L. We also found an increase in volume of distribution: + 18.9% in group HA, and + 35.8% in group HC when measured in plasma, and + 16.9% in group HA and + 18.8% in group HC when measured in whole blood. Lithium uptake by the erythrocytes increases: the value of 36.7 +/- 22.7% in Group L rose to 54.8 +/- 21.1% and to 54.6 +/- 24.2% in groups HA and HC, respectively. Total clearance decreases at high altitude, though the differences were significant only in group HC (37%).

Conclusion: Results indicate that exposure to H produces alterations in the pharmacokinetics of lithium and that these variations may be clinically relevant.