Elimination of stabilised hyaluronan from the knee joint in healthy men

Clin Pharmacokinet. 2002;41(8):603-13. doi: 10.2165/00003088-200241080-00004.


Objective: To investigate the elimination of stabilised hyaluronan following intra-articular injection into the knee joint.

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

Participants: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacokinetics*
  • Adult
  • Excipients / chemistry
  • Half-Life
  • Humans
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacokinetics*
  • Injections, Intra-Articular
  • Iodine Radioisotopes
  • Knee Joint / diagnostic imaging
  • Knee Joint / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Radionuclide Imaging
  • Tissue Distribution


  • Adjuvants, Immunologic
  • Excipients
  • Iodine Radioisotopes
  • Hyaluronic Acid