title: Age affects the pharmacokinetics of inhaled anesthetics in humans.
abstract: To define the effect of aging on the pharmacokinetics of volatile anesthetics, we determined the end-tidal and mixed expired anesthetic concentrations of isoflurane, enflurane, halothane, and methoxyflurane during 30 min of simultaneous administration and for 5-12 days of elimination in seven healthy young patients (31 +/- 1.8 yr [mean +/- SEM]) and in 11 healthy aged patients (73.2 +/- 3.1 yr [mean +/- SEM]). A five-compartment mammillary function was fit to the end-tidal and mixed expired anesthetic elimination data simultaneously using ordinary least-squares analysis. We assumed the compartments to represent the following tissue groups: lungs and pulmonary capillary blood (V1), vessel-rich tissues (i.e., liver, heart, kidneys, and brain) muscle, an unidentified fourth compartment, perhaps fat adjacent to well-perfused tissues, and fat tissues. The tissue volumes and perfusions estimated for these compartments approximated values from the literature. In general, the volume of the fourth and fifth compartments increased with age, and perfusion to the second and fifth compartments decreased with age. Aging delayed anesthetic elimination and increased the apparent volume of distribution at steady state. These observations are compatible with decreased tissue perfusion and an increase in the ratio of fat/lean body weight in the elderly. Our mammillary analysis described the behavior of less soluble anesthetics such as isoflurane well, but that of highly soluble anesthetics such as methoxyflurane less well.
authors.affiliation: Department of Anesthesiology, University of Pittsburgh, Pennsylvania.
authors.forename: D P
authors.initials: DP
authors.lastname: Strum
authors.forename: E I
authors.initials: EI
authors.lastname: Eger
authors.forename: J D
authors.initials: JD
authors.lastname: Unadkat
authors.forename: B H
authors.initials: BH
authors.lastname: Johnson
authors.forename: R L
authors.initials: RL
authors.lastname: Carpenter
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000769:Anesthesia, Inhalation; D000777:Anesthetics / Q000493:pharmacokinetics*; D001835:Body Weight; D004737:Enflurane / Q000493:pharmacokinetics; D005260:Female; D006221:Halothane / Q000493:pharmacokinetics; D006801:Humans; D007530:Isoflurane / Q000493:pharmacokinetics; D008297:Male; D008733:Methoxyflurane / Q000493:pharmacokinetics; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000777:Anesthetics; D008733:Methoxyflurane; D004737:Enflurane; D007530:Isoflurane; D006221:Halothane