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Metabolic fate of a high molecular-weight s odium hyaluronate (SL-1010), a highly purified preparation from the culture medium of Streptococcus zooepidemicus, was studied in rabbits after intraarticular injection into the knee. 1. Radioactivity in the synovial fluid was eliminated biphasically with apparent half-life of 32hr during the first phase, when most radioactivity was eliminated. Gel filtration patterns showed that the SL-1010, a low molecular-weight fraction, was eliminated from the joint cavity faster than the high molecular-weight fraction. 2. In joint region, higher radioactivity was detected in the synovial tissue, and much less radioactivity was observed in the articular cartilage, meniscus and ligament. Total radioactivity in the rest of the whole body was less than that in the knee joint. The highest levels were in Harder's gland, and followed by reticuloendothelial tissues, such as the liver and spleen. Radioactivity was much lower in other tissues including plasma, and there was no radioactivity in the sodium hyaluronate (HA) fraction isolated from liver and plasma. Gel filtraton patterns showed that the main molecular-weight distribution of HA isolated from synovial tissue 24, 48 and 72hr after injection was similar to that of 14C-SL-1010 except for a small quantities of a low molecular-weight fraction. This suggests that 14C-SL-1010 was only slightly metabolized in the synovial tissue. 3. The route of elimination of 14C-SL-1010 from the joint cavity was mainly via the lymphatic system, since any time after elimination of 14C-SL-1010 from the joint cavity the level of radioactivity in the iliac lymph node was much higher than that in the liver. The radioactivity derived from HA in the iliac lymph nodes 24hr after injection and identified as HA-specific hyaluronidase treatment, was 5.6 to 11.7% of the total radioactivity. In in vitro study, metabolic activity in the lymph node was higher than that in the liver. It is suggested that most of the 14C-SL-1010 injected into the knee joint was eliminated and was mainly metabolized in the lymphatic system. 4. Excretion of radioactivity at 144 hr was 70, 3.5 and 0.8% in expired air, urine and feces, respectively. 5. Sex related differences in the distribution of radioactivity either in blood or plasma were negligible.

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Studies on the Metabolic Fate of Sodium Hyaluronate (SL-1010) after Intra-articular Administration. (I). Distribution, Metabolism and Excretion after Intra-articular Injection into Rabbit Knee.