Studies on the kinetics, metabolism and re-utilisation after intra- articular administration of hyaluronan to rabbits

The pharmacokinetics of hyaluronan (HA) (CAS 9004-61-9) was measured after intra-articular (i.a.) injection of 1 mg/kg of ¹⁴C-glucose-labelled HA (¹⁴C-HA) (i.e. 2,000 kDa) into the knee joint cavity of rabbits. The movement of HA from the cavity into the systemic circulation was assessed by measuring its concentration in blood and its residue in the cavity. I.a. HA moved into, and disappeared from, the bloodstream at a first-order rate. Synovial fluid, synovial membrane and articular cartilage specimens were taken 24 and 72 h post-injection, and the molecular weight (MW) of HA fractions were measured by using gel filtration chromatography (GFC) using radioactive fractions of known molecular sizes (i.e. 2,000 kDa, 300 kDa and 50 kDa). The radioactivity distribution of synovial fluid had a peak at a 2,000 kDa-equivalent fraction at both 24 and 72 h post-injection, while synovial membrane had a peak at a 300 kDa-equivalent fraction 24 h post- injection and at a 50 kDa equivalent fraction 72 h post-injection. The radioactivity distribution pattern of articular cartilage showed peaks corresponding to 2,000-300 kDa 24 h post-injection and to 50 kDa 72 h post- injection. The in vivo re-utilisation of i.a. HA was investigated by assessing radioactivity in the acid soluble, lipid and protein fractions of plasma, blood cells and liver 72 h post-injection. Results show that HA was broken down into C₁ units (carbon cycle) before being re-used as an in vivo constituent in the body.