Peritoneal lavage fluid protease levels after in vivo administration of tolmetin in hyaluronic acid

Tolmetin sodium in a hyaluronic acid carrier (tolmetin-HA) was previously shown to reduce adhesion formation and alter the rate and extent to which wound repair cells enter the peritoneal cavity after surgery. In this study, the effect of tolmetin-HA on the levels of protease activities present in lavage fluid from the peritoneal cavity was determined at various postsurgical times. Collagenase activity in peritoneal lavage fluid was suppressed at 6, 12, and 24 hr after administration of tolmetin-HA in comparison to control. Elastase activity levels were biphasic with peak levels at 6 and 72 hr in lavage fluid from controls compared to peak levels at 6 and 48 hr in lavage fluid from treated rabbits. Plasminogen activator activity present in lavage fluid was significantly decreased at 48 hr after surgery in the tolmetin-HA-treated rabbits compared to controls. However, no alteration in the level of plasminogen activator inhibitor activity was observed in either the tolmetin-HA-treated or control rabbits. These data suggest that tolmetin-HA treatment altered the levels of neutral protease activity present in the peritoneal cavity and may therefore effect the proteolytic potential in the peritoneal cavity after surgery.