Clearance kinetics of a hylan-based viscosupplement after intra-articular and intravenous administration in animal models.

Abstract

Clearance of hylan fluid and hylan gel, components of the hyaluronan (HA)-derived viscosupplement hylan G-F 20, following intra-articular injection into normal, healthy rabbits was evaluated. Radiolabeled hylan G-F 20 was injected at a volume of 0.3 mL into both knee joints of 12 rabbits. At sacrifice, synovial fluid, joint tissues, blood, popliteal lymph nodes, liver, spleen, kidney, and lung were analyzed for radioactivity. The half-life of the fluid component, a high-molecular weight hylan, was 1.5 ± 0.2 days while the half-life of the hylan gel component, a crosslinked hylan, was 8.8 ± 0.9 days. There was no radioactivity detected in the blood or the major internal organs following intra-articular injection. A rat model was used to evaluate the clearance of a large intravenous bolus of solubilized hylan gel. No accumulation of hylan gel degradation products was observed in any major organs and the half-life of hylan elimination from the blood was within normal ranges for HA elimination. The dosing used in the nonclinical rabbit intra-articular study was equivalent (v/w) to a single 6 mL dose in humans. These results are consistent with the current clinical data that demonstrates safety and effectiveness of an increased volume of hylan G-F 20 injected into the osteoarthritis knee.