PHARMACOKINETICS OF MEPERIDINE IN HEALTHY-VOLUNTEERS AFTER SHORT-TERMAND LONG-TERM EXPOSURE TO HIGH-ALTITUDE

Increased numbers of erythrocytes have been shown ex vivo to increase meperidine uptake, and one of the major physiologic changes that occur s at high altitude is an increase in hematocrit and erythrocytes. A st udy was therefore conducted to evaluate the effects of high altitude o n the pharmacokinetics of meperidine. Intramuscular doses (0.75 mg/kg) of meperidine were given to three groups of healthy volunteers (age r ange, 18-20 years): participants living at sea level (group L), those same participants the day after arrival at high altitude (4,360 m; gro up HA), and participants who had lived at high altitude for greater th an or equal to 10 months (group HG). Blood samples were collected for 12 hours after drug administration. Meperidine was measured in whole b lood, plasma, and plasma water. Elimination rate constant (lambda(z)) and clearance uncorrected for bioavailability (Cl/F) were significantl y lower at high altitudes than at sea level in plasma (HA and HC) and in whole blood (HA only). Mean residence time (MRT) was significantly higher at high altitudes than at sea level in plasma (HA and HC) and i n whole blood (HA only). Hematocrit was significantly increased at bot h rime points at high altitude in comparison to values at sea level, a nd was also higher after a long-term stay at high altitude than after arrival at high altitude. Erythrocyte binding increased significantly from 41.3% at sea level to 43.8% at arrival at high altitude to 50.9% after a long-term stay ay high altitude. The extent of protein binding tended to decrease with high altitude, but this decrease was not sign ificant. Free concentrations of meperidine in plasma water measured 1, 2, and 4 hours after administration were significantly increased afte r 2 and 4 hours.