Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison

Table 4

Mean pharmacokinetic parameters for bupivacaine in dogs receiving twice-weekly subcutaneous bolus doses of DepoFoam bupivacaine (EXPAREL) or bupivacaine HCl solution (mean ±SD; N = 3/sex/group).

Dosing day	Treatment	Bupi (mg/kg)	𝐴𝑈𝐶0-72hr; (ng⋅hr/mL)	𝐴𝑈𝐶0-72hr/dose; (ng⋅hr/mL)	C max(ng/mL)	C max/dose (ng/mL)	t 1/2^a (hr)	t max (hr)
1	Bupivacaine HCl	9	9,720 ± 1,860	1,080 ± 207	1,420 ± 355	158 ± 39.5	16.9 ± 6.05	0.500 ± 0
	EXPAREL	9	9,100 ± 4,460	1,010 ± 495	488 ± 335	54.2 ± 37.2	59.5 ± 49.1 ^a	0.500 ± 0
		18	12,800 ±2,020	711± 112	560 ± 299	31.1 ± 16.6	104 ± 105	0.500 ± 0
		30	25,600 ±8,160	853± 272	633 ± 280	21.1 ± 9.34	31.8^a	48.1± 30.2
25	Bupivacaine HCl	9	9,120 ± 4,090	1,010 ± 455	1,990 ± 304	221 ± 33.8	10.1 ± 8.54	0.500 ± 0
	EXPAREL	9	17,300 ± 8,710	1,920 ± 968	1,200 ± 301	133 ± 33.4	36.2 ± 12.4	0.500 ± 0
		18	24,300 ± 8,960	1,350 ± 498	1,310 ± 521	72.6 ± 28.9	25.7 ± 8.15	0.750 ± 0.610
		30	43,800± 23,300	1,460 ± 777	910 ± 433	30.3 ± 14.4	43.9 ± 12.7^a	12.8 ± 18.0

^aParameter not calculated in one animal (9 mg/kg, Day 1), four animals (30 mg/kg, Day 1), and one animal (30 mg/kg, Day 25) due to insufficient number of data points during the terminal phase to estimate a reliable plasma half-life.