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KMID : 1034820140100030319
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Molecular & Cellular Toxicology
2014 Volume.10 No. 3 p.319 ~ p.328
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Four-week toxicity and toxicokinetics of piroxicam and hyaluronic acid combination following intra-articular injection in normal rats
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Park Chan-Woong
Ma Kyung-Wan
Jang Sun-Woo
Son Mi-Won
Kang Myung-Joo
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Abstract
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The 4-week toxicity and toxicokinetics of a piroxicam (PX)/ hyaluronic acid (HA) combination were assessed in normal rats after intra-articular (IA) injection into the knee. Rats received PX or HA alone or in combination intra-articularly once a week for 4 weeks at an each dose of 4 mg/kg, a maximum feasible dose. There were transient and reversible changes in food consumption, hematology and serum chemistry, and minimal hypertrophy and hyperplasia of synovial cells on histopathological observation. However, no increase in toxicity was observed with the combination of PX and HA with no dose-dependent manner. Systemic exposure of HA and PX was similar throughout the experimental period when administered alone or concurrently, indicating that there were no pharmacokinetic drug-drug interactions, affecting exposure of either therapeutic agent. This study will support future studies of the IA combination of PX and HA in osteoarthritis-induced animal models and even patients.
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KEYWORD
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Piroxicam, Hyaluronic acid, 4-week toxicity, Toxiokinetics, Intra-articular injection
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