DepoFoam Bupivacaine (DB; EXPAREL™; Bupivacaine Liposome Extended-Release Injectable Suspension) Exhibits Pharmacokinetic Properties Consistent With Sustained-Release Characteristics

 

Liposomal drug containing formulations are designed to provide slow release of drug over an extended period of time, thus extending duration while diminishing high plasma levels. We conducted a cross-study analysis of the pharmacokinetic properties of DepoFoam Bupivacaine (DB; proposed proprietary name, EXPAREL™), an extended-release multivesicular liposomal formulation of bupivacaine in DepoFoam, given as a single injection.

Methods:
Pooled data from 446 individuals (age 18–85; 63% male) from eleven Phase 1–3 studies who received either DB or bupivacaine HCl were analyzed for pharmacokinetic parameters including Tmax, t1/2, and Cmax.

Routes of administration included wound infiltration, subcutaneous, epidural, and nerve block.

Surgical models included hemorrhoidectomy, herniorraphy, bunionectomy, and total knee arthroplasty.

Doses ranged from 75–750 mg.

Results:
DB demonstrated bimodal peak concentrations at 0.25–2 hours (likely due to the small amount of extraliposomal bupivacaine present in the formulation) and at 12–24 hours after injection (resulting from the slow and prolonged release of bupivacaine from the DepoFoam). In contrast, bupivacaine HCl peaked once at 0.25–2 hours with a rapid decline toward zero. After wound infiltration, DB exhibited a t1/2 of 34.1 hours and a highest mean plasma Cmax of 935 ng/mL (2- to 4-fold below bupivacaine’s minimal toxicity thresholds), obtained after local administration of 600 mg DB.

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