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.

Osteoarthritis is the most common joint disorder worldwide and one of the leading causes of disability in the elderly. We have reported that the novel sodium hyaluronate derivative chemically linked with diclofenac (DF), diclofenac etalhyaluronate (SI-613), exerted a potent and long-lasting analgesic eŠect in experimental arthritis models. In this study, we evaluated the properties of residual SI-613 in the knee joint after an intra-articular (IA) administration. After IA administration of ‰uorescent labeled SI-613 (FA-SI-613) or ‰uorescent labeled hyaluronic acid (FA-HA) to rabbits, ‰uorescence intensities in the synovial membrane and cartilage were higher in the FA-SI-613 group until 7 d after administration than in the FA-HA group. After IA administration of radiolabeled SI-613 ( 14 C-SI-613) to rabbits, the radioactivity remained in the joint cavity and the joint tissues such as synovial membrane and cartilage until 84 d after administration. This residual radioactivity was identiˆed mainly as HA linked with DF, since 14 C-SI-613 was labeled at the benzene ring of DF and since more DF-linked HA oligomer was detected on metabolite analysis than free DF in the synovial membrane and synovial lavage ‰uid up to 28 d after administration. These results suggested that intra-articularly administered SI-613 remained for a longer time in the joint as HA linked with DF than when HA was administered. Therefore, SI-613 was considered to prolong the pharmacological eŠects of both HA and DF by remaining in the joint as HA linked with DF.

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Residual Property of SI-613, a Novel Drug for Osteoarthritis, in Knee Joint

Ishii

Yoshioka

Morita

2020

YAKUGAKU ZASSHI

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

Momose¹,

Mukai²,

Shigematsu³

et al. 1993

Drug Metabolism and Pharmacokinetics

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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.

Cited by 2 publications

References 5 publications

Residual Property of SI-613, a Novel Drug for Osteoarthritis, in Knee Joint

Residual Property of SI-613, a Novel Drug for Osteoarthritis, in Knee Joint

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

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