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

Table 3

Mean pharmacokinetic parameters for bupivacaine in rabbits 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 (hr)	t max(hr)
1	Bupivacaine HCl	9	2,350 ± 587	261 ± 65.2	396 ± 315	44.1 ± 35.0	9.57 ± 3.10	2.50 ± 4.66
	EXPAREL	9	2,520 ± 429	280 ± 47.6	213 ± 145	23.7 ± 16.1	42.0 ± 26.4	1.42 ± 1.39
		18	3,750 ±503	208 ± 27.9	147± 59.6	8.18 ± 3.29	48.2 ± 32.4	3.33 ± 3.61
		30	4,710 ± 1150	157 ± 38.5	94.4 ± 45.2	3.15 ± 1.51	150 ± 78.8	26.3 ± 24.2
25	Bupivacaine HCl	9	2,060 ± 454	228 ± 50.5	218 ± 122	24.3 ± 13.6	11.2 ± 4.76	2.67 ± 4.58
	EXPAREL	9	2,380 ± 1170	264 ± 130	338 ± 136	37.5 ± 15.2	14.5 ± 9.25	0.580 ± 0.200
		18	5,810 ± 426	323 ± 23.7	347 ± 210	19.3 ± 11.7	17.2 ± 7.06	4.67 ± 9.47
		30^a	10,100 ± 4590	336 ± 153	292 ± 233	9.73 ± 7.76	62.9 ± 42.6	7.50 ± 6.16

^aOne female died prior to Day 25.