Effects of sodium taurocholate on the absorption of inhaled 99mTc-DTPA.
OBJECTIVE
The effects of a natural surface-active agent, sodium taurocholate (NaTC), on the absorption of a hydrophilic solute, technetium-99m-labelled diethylene triamine pentaacetic acid (99mTc-DTPA), deposited at various sites within the airways were evaluated in this open, cross-over, and single-dose study.


METHODS
Nine healthy non-smokers received 99mTc-DTPA with or without the addition of NaTC, administered as an oropharyngeal aerosol and as nebulized large and fine droplet-sized pulmonary aerosols delivered by Pari and UltraVent nebulizers inhaled at fairly rapid and slow flows, respectively. Plasma concentration versus time profiles and 24-h urinary excretion of radioactivity were assessed. Further, 99mTc-labelled human serum albumin nanocolloidal particles (99mTc-Nanocoll) were administered with or without NaTC by Pari and followed by repeated chest gamma-imaging.


RESULTS
NaTC changed no pharmacokinetic parameters for oropharyngeal 99mTc-DTPA. Independent of intrapulmonary 99mTc-DTPA deposition pattern, NaTC reduced Tmax (Pari: -0.8 h; UltraVent: -1.5 h) and mean absorption time (MAT) (-0.4 h; -0.7 h), and increased bioavailability (+13%; +44%) and dose-adjusted Cmax (+54%; +103%). NaTC decreased the pulmonary 99mTc-Nanocoll disappearance half-life from 8 h and 45 min to 4 h and 19 min.


CONCLUSIONS
Our findings suggest that NaTC increases both rate and extent of 99mTc-DTPA absorption throughout the lower airways, without changing 99mTc-DTPA absorption in the oral cavity.
Bondesson
Eva
E
AstraZeneca R&D Lund, SE-221 87, Lund, Sweden. Eva.Bondesson@astrazeneca.com
Bengtsson
Thomas
T
Nilsson
Lars-Erik
LE
Wollmer
Per
P
D000280:Administration, Inhalation; D000328:Adult; D001682:Biological Availability; D006207:Half-Life; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011786:Quality Control; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013656:Taurocholic Acid / Q000494:pharmacology*; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013909:Thorax / Q000000981:diagnostic imaging
D019275:Radiopharmaceuticals; D013656:Taurocholic Acid; D016284:Technetium Tc 99m Pentetate