Elimination of stabilised hyaluronan from the knee joint in healthy men.
OBJECTIVE
To investigate the elimination of stabilised hyaluronan following intra-articular injection into the knee joint.


METHODS
This was a single-centre, single-dose study in healthy human volunteers.


METHODS
Six healthy men, aged 28 to 47 (mean 38) years, were enrolled in the study.


METHODS
Subjects received a single intra-articular injection (3ml; 20 mg/ml) of (131)I-labelled non-animal stabilised hyaluronic acid (NASHA). Radioactivity in the knee, blood, urine and over the liver was measured with gamma counters for 3 weeks post-injection; magnetic resonance and gamma camera imaging of the knee were also performed at 24 hours post-injection. Radioactivity uptake data were tested for conformity of fit to different mathematical models.


RESULTS
Elimination of (131)I-labelled NASHA from the knee was characterised by a fast initial phase and a slow late phase, and conformed to a three-exponential-function model with elimination half-lives of 1.5 hours, 1.5 days and 4 weeks. Radioactivity distribution within the knee joint was homogenous, and no local leakage was observed. Hepatic radioactivity uptake was low, but significantly above background levels, for the first 2 days post-injection, before declining to background levels. Visual imaging indicated an increase in intra-articular fluid volume at 24 hours post-injection.


CONCLUSIONS
The elimination kinetics of (131)I-labelled NASHA from the human knee joint were described by three distinct phases, with half-times of 1.5 hours, 1.5 days and 4 weeks. Most likely, the last value reflects the true half-life of NASHA following intra-articular injection since the labelling method used causes minimal modification of hyaluronan.
Lindqvist
Ulla
U
Department of Medical Sciences, Rheumatology, University Hospital, Uppsala SE-751 85, Sweden.
Tolmachev
Vladimir
V
Kairemo
Kalevi
K
Aström
Gunnar
G
Jonsson
Eva
E
Lundqvist
Hans
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000328:Adult; D005079:Excipients / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007270:Injections, Intra-Articular; D007457:Iodine Radioisotopes; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D000276:Adjuvants, Immunologic; D005079:Excipients; D007457:Iodine Radioisotopes; D006820:Hyaluronic Acid