title: Pharmacokinetics of meperidine in healthy volunteers after short- and long-term exposure to high altitude.
abstract: Increased numbers of erythrocytes have been shown ex vivo to increase meperidine uptake, and one of the major physiologic changes that occurs at high altitude is an increase in hematocrit and erythrocytes. A study was therefore conducted to evaluate the effects of high altitude on the pharmacokinetics of meperidine. Intramuscular doses (0.75 mg/kg) of meperidine were given to three groups of healthy volunteers (age range, 18-20 years): participants living at sea level (group L), those same participants the day after arrival at high altitude (4,360 m; group HA), and participants who had lived at high altitude for > or = 10 months (group HC). Blood samples were collected for 12 hours after drug administration. Meperidine was measured in whole blood, plasma, and plasma water. Elimination rate constant (lambda z) and clearance uncorrected for bioavailability (Cl/F) were significantly 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 in whole blood (HA only). Hematocrit was significantly increased at both time points at high altitude in comparison to values at sea level, and 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 at high altitude. The extent of protein binding tended to decrease with high altitude, but this decrease was not significant. Free concentrations of meperidine in plasma water measured 1, 2, and 4 hours after administration were significantly increased after 2 and 4 hours.
authors.affiliation: University of Cincinnati, Ohio, USA.
authors.forename: W A
authors.initials: WA
authors.lastname: Ritschel
authors.forename: C
authors.initials: C
authors.lastname: Paulos
authors.forename: A
authors.initials: A
authors.lastname: Arancibia
authors.forename: M
authors.initials: M
authors.lastname: Pezzani
authors.forename: M A
authors.initials: MA
authors.lastname: Agrawal
authors.forename: K M
authors.initials: KM
authors.lastname: Wetzelsberger
authors.forename: P W
authors.initials: PW
authors.lastname: Lücker
mesh_terms: D000293:Adolescent; D000328:Adult; D000531:Altitude; D000532:Altitude Sickness / Q000503:physiopathology; D000701:Analgesics, Opioid / Q000378:metabolism / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006400:Hematocrit; D006801:Humans; D007273:Injections, Intramuscular; D008614:Meperidine / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D008614:Meperidine