title: Safety aspects and pharmacokinetics of inhaled aerosolized gadolinium.
abstract: This study evaluated the pharmacokinetics and potential toxicity of inhaled aerosolized gadopentetate dimeglumine. The pharmacokinetics were evaluated with in vitro relaxometry of the lungs, blood, urine, and liver before and for up to 36 hours after a 5-minute inhalation of aerosolized gadopentetate dimeglumine (0.25 mol/L). For assessment of potential toxicity, hemodynamic variables were monitored during and for 10 minutes after inhalation. Extravascular lung water was measured before and after exposure. Finally, the potential for tissue damage was evaluated histologically. Pulmonary clearance of aerosolized gadopentetate dimeglumine was monoexponential with a half-time of 2.16 hours. Aerosolized gadopentetate dimeglumine was excreted through the kidneys, as shown by the decrease in urinary T1. Renal elimination was completed by 30 hours. No acute hemodynamic effect, histologic change, or induction of edema was demonstrated. This study shows that inhalation of aerosolized gadopentetate dimeglumine is well tolerated in rats and favors the further evaluation of this administration route, including clinical trials.
authors.affiliation: Department of Radiology, University of California, San Francisco 94143-0628.
authors.forename: Y
authors.initials: Y
authors.lastname: Berthezène
authors.forename: A
authors.initials: A
authors.lastname: Mühler
authors.forename: P
authors.initials: P
authors.lastname: Lang
authors.forename: D M
authors.initials: DM
authors.lastname: Shames
authors.forename: O
authors.initials: O
authors.lastname: Clément
authors.forename: W
authors.initials: W
authors.lastname: Rosenau
authors.forename: R
authors.initials: R
authors.lastname: Kuwatsuru
authors.forename: R C
authors.initials: RC
authors.lastname: Brasch
mesh_terms: D000336:Aerosols; D000818:Animals; D003287:Contrast Media / Q000633:toxicity*; D004338:Drug Combinations; D015633:Extravascular Lung Water / Q000187:drug effects; D005260:Female; D005682:Gadolinium / Q000633:toxicity; D019786:Gadolinium DTPA; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging; D008536:Meglumine / Q000633:toxicity; D009942:Organometallic Compounds / Q000633:toxicity; D004369:Pentetic Acid / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000336:Aerosols; D003287:Contrast Media; D004338:Drug Combinations; D009942:Organometallic Compounds; D008536:Meglumine; D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA