Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs.
The purpose of this study was to determine the absorption, distribution and excretion of (99m)technetium-labeled, high-molecular-weight hyaluronan (((99m)Tc-HA) and (99m)technetium pertechnetate ((99m)Tc-P) after single dose, oral administration to Wistar rats and Beagle dogs. A pilot study utilized (99m)Tc-HA alone, and a second confirmatory study compared uptake of labeled (99m)Tc-HA with (99m)Tc-P. Urinary and fecal excretion after (99m)Tc-HA ingestion by rats showed 86.7-95.6% of radioactivity was recovered, almost all in feces. All tissues examined showed incorporation of radioactivity from (99m)Tc-HA starting at 15 min and persisting for 48 h, in a pattern significantly different from (99m)Tc-P. Whole-body scintigraphs and close-ups of the ventral chest region showed nonalimentary radioactivity from (99m)Tc-HA concentrated in joints, vertebrae and salivary glands four hours after administration. Autoradiography of skin, bone and joint tissue pieces after 24 h showed incorporation of radioactivity from (99m)Tc-HA, but not from (99m)Tc-P. Conversely, absorption, distribution and excretion of (99m)Tc was completely different from (99m)Tc-HA, showing an expected pattern of rapid absorption and excretion in urine, with accumulation in thyroid glands, stomach, kidney and bladder. This report presents the first evidence for uptake and distribution to connective tissues of orally administered, high-molecular-weight HA.
Balogh
Lajos
L
Department of Applied Radioisotopes, National FJC Research Institute for Radiobiology and Radiohygiene, Fodor Jozsef National Center of Health, Budapest, Hungary, .
Polyak
Andras
A
Mathe
Domokos
D
Kiraly
Reka
R
Thuroczy
Juliana
J
Terez
Marian
M
Janoki
Gyozo
G
Ting
Yaoting
Y
Bucci
Luke R
LR
Schauss
Alexander G
AG
D000042:Absorption; D000818:Animals; D004285:Dogs; D005243:Feces / Q000737:chemistry; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine; D007553:Isotope Labeling; D008970:Molecular Weight; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium; D014018:Tissue Distribution
D013667:Technetium; D006820:Hyaluronic Acid