Alterations of drug disposition in high altitude

Resumen

Exposure of the human body to high altitude (H) results in significant physiologic changes and may precipitate mountain sickness, ranging from mild symptoms above 2500 m to severe symptoms above 4000 m, and coma a teven higher altitude. In a previous study in our labs we found et vivo an increase in meperidine (M) upteke wilh increase in number of erythrocytes (RBG). One of the major physiologic changes at H is a increase in hematocrit and RBC. The study was carried out in three groups of healthy volunteers (18-2' y): at sea level (L), at 4360 m the day after arrival at H (HA), and at 4360 m in subjects residing > 10 mo at H (HC), 0.75 mglkg of M was administered I.M. between 8-9 a.m. Blood was collected for 12 h. M was measured in whole blood (WB), plasma (P) and plasma -water (PW). The pharmacokinetic parameters derived from curve-fitting were analyzed by ANOVA. Significant changes were found in P and (WB) for λ_z ↓ L vs HA (L vs HA), L vs HC; CL/F ↓ L vs HA (L vs HA), L vs HC, and MRT ↑ L vs HA (L vs HA), L vs HC. The hematocrit significantly increased L vs HA, L vs HC end HA vs HC from 43.3 to 46.4 to 53.4%. The RBC binding significantly increase from 42.3% at L to 43.8% at HA to 50.9% at GC. The extent 01 protein binding shows a trend to decrease with H, however, it is not significant. Free M concentration in PW measured after 1,2, and 4 h was significently increased after 2 and 4 h.