Table 1.

IV/IA study designs

Test material	Dose 1	Dose 2	Dose 3	Dose 4
IV/IA dose-finding study
IV bupivacaine HCl 7.5 mg/mL	1.0 mg/kg (Animal 1)	1.0 mg/kg (Animal 3) 1.8 mg/kg (Animal 1)	2.5 mg/kg (Animal 1)	1.8 mg/kg (Animal 2)
IV liposome bupivacaine 13.3 mg/mL	4.5 mg/kg (Animal 2)	9.0 mg/kg (Animal 2)	9.0 mg/kg (Animal 5)	4.5 mg/kg (Animal 1)
IA bupivacaine HCl 7.5 mg/mL	1.0 mg/kg (Animal 3)		0.1 mg/kg (Animal 3)
IA liposome bupivacaine 13.3 mg/mL	4.5 mg/kg (Animal 4)	9.0 mg/kg (Animal 4)		4.5 mg/kg (Animal 3)
	Dose level (mg/kg)	Dose concentration (mg/mL)	Number of animals, main study	Number of animals, recovery study
IV/IA expanded study
IV saline control	0	0	3 male/3 female	2 male/2 female
IV bupivacaine HCl	1.5/0.75a	7.5	3 male/3 female	2 male/2 female
IV liposome bupivacaine	1.5	13.3	3 male/3 female	2 male/2 female
IV liposome bupivacaine	4.5	13.3	3 male/3 female	2 male/2 female
IA saline control	0	0	3 male/3 female	2 male/2 female
IA bupivacaine HCl	0.1	7.5	3 male/3 female	2 male/2 female
IA liposome bupivacaine	1.5	13.3	3 male/3 female	2 male/2 female
IA liposome bupivacaine	4.5/3.0b	13.3	3 male/3 female	2 male/2 female

Notes:

^aAnimals in the recovery study received 1.5 mg/kg; this dose was reduced to 0.75 mg/kg for animals in the main study based on observed clinical signs;

^banimals in the recovery study received 4.5 mg/kg; this dose was reduced to 3.0 mg/kg for animals in the main study based on observed clinical signs.

Abbreviations: IA, intra-arterial; IV, intravenous.