Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison
| Autor: | Dean Haan, Phaedra I. Cole, Douglas E. Rickert, Paul E. Ross, Brigitte M. Richard, Keith Nelson, Paul E. Newton, Laura R. Ott, Marlon C. Rebelatto, Abram N. Brubaker |
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| Rok vydání: | 2011 |
| Předmět: |
Bupivacaine
Article Subject business.industry lcsh:RS1-441 Pharmacology 3. Good health lcsh:Pharmacy and materia medica Granulomatous inflammation 03 medical and health sciences Subcutaneous injection 0302 clinical medicine 030202 anesthesiology Toxicity Bupivacaine hcl medicine business 030217 neurology & neurosurgery Research Article medicine.drug |
| Zdroj: | Journal of Drug Delivery, Vol 2011 (2011) Journal of Drug Delivery |
| ISSN: | 2090-3022 2090-3014 |
| Popis: | EXPAREL (bupivacaine extended-release liposome injection), DepoFoam bupivacaine, is in development for prolonged postsurgical analgesia. Repeat-dose toxicity studies were conducted in rabbits and dogs to compare the potential local and systemic toxicities of EXPAREL and bupivacaine HCl (Bsol), and the reversibility of any effects. Dogs tolerated much larger doses than rabbits. EXPAREL-related minimal-to-moderate granulomatous inflammation was noted at the injection sites. In recovery animals, the granulomatous inflammation was observed less frequently and was characterized by an increased number of multinucleated giant cells. These effects were considered a normal response to liposomes and nonadverse. Rabbits are more sensitive than dogs. In rabbits, convulsions were noted with EXPAREL and more frequently with Bsol; a NOAEL was not identified. In dogs, EXPAREL was well tolerated (NOAEL > 30 mg/kg/dose). The cumulative exposure of EXPAREL in these studies is well in excess of the proposed maximum single-dose exposure that is intended in humans. |
| Databáze: | OpenAIRE |
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