DepoFoam® Bupivacaine (EXPARELTM) is Compatible Following Lidocaine: Pharmacokinetic Study in Mini‐pigs

• Published in: The FASEB journal 2011-04, Vol.25 (S1), p.lb392-lb392
• Main Authors: Richard, Brigitte M, Rickert, Doug E, Doolittle, Danette, Mize, Amy, Liu, Jason, Lawson, Charles F
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.25.1_supplement.lb392

DepoFoam bupivacaine (DB; bupivacaine extended‐release liposome injection) is in development for prolonged postsurgical analgesia via wound infiltration (WI). Lidocaine with epinephrine (lido/epi) is commonly used for WI prior to surgery. DepoFoam product, DepoDur® can exchange its drug load with lido (ref. DepoDur® USPI) and we explored this potential with DB. Sixty (60) male Yucatan Swine were randomized into 20 groups (N=3/group). DB (2 or 4 mg/kg) and/or lidocaine HCl solution 1% or 2% (with epinephrine 1:200,000) were injected subcutaneously along a 5‐cm virtual incision line. Time intervals (5, 10, 20 or 40 minutes) between administration of lido/epi and DB were tested. Plasma concentrations of bupivacaine (bup) and lido were measured simultaneously by a LC‐MS/MS assay. Systemic exposure to lido was increased (AUC0–24hr by 48%; Cmax by 1,640%) when lido (4 mg/kg) was followed 5 minutes later by DB (4 mg/kg) compared to lido/epi alone. The systemic exposure to bup was increased (AUC0–24hr by 50 – 95%; Cmax by 67 – 1000%) when lido (4 mg/kg) was followed 5 or 10 minutes later by DB (4 mg/kg) compared to DB alone. While DB should not be admixed with lidocaine, this study shows that DB may be locally administered after at least 20 minutes following local administration of lido with minimal potential for a clinically relevant interaction. Source of Research Support: Pacira Pharmaceuticals, Inc.