The effect of local/topical analgesics on incisional pain in a pig model

Figures & data

Table 1 Details of drug concentration, dosing volume and final dose per animal

Drug name	Active ingredient	Concentration	Volume of injection	Final dose
Exparel	Bupivacaine	233 mg/mL	1.3 mL	~300 mg/animal
		100 mg/mL	1 mL	100 mg/animal
		30 mg/mL	1 mL	30 mg/animal
Marcaine	Bupivacaine	5 mg/mL	6 mL	30 mg/animal
			2 mL	10 mg/animal
Naropin	Ropivacaine	10 mg/mL	5 mL	50 mg/animal
			2.5 mL	25 mg/animal
Saline	–	–	6 mL	–

Table 2 Study design, study day 0 is the surgery day

Study time point (days)	Activity
–5 to –1	Acclimation and habituation
–1	Von Frey testing (baseline)
0	Surgery (SI or SMI) Treatment Von Frey testing at 3, 5 and 12 h post SI model/1, 3, 5 and 7 h post SMI model
1	Von Frey testing at 24 h post surgery

Abbreviations: SI, skin incision; SMI, skin and muscle incision.

Figure 1 Withdrawal force following treatment with Exparel, the liposomal formulation of bupivacaine (A) and Marcaine, a commercial bupivacaine solution (B) in the SMI model.

Notes: The activity of both drugs was dose related. The duration of activity of Exparel was longer than that measured for Marcaine. Both drugs were not active 24 h post dosing. **p<0.001 vs. vehicle group.
Abbreviation: SMI, skin and muscle incision.

Figure 2 Calculations of AUC expressing the level and duration of activity of the drugs.

Notes: The results presented in this figure show that treatment with Exparel at the highest dose used in the clinic had a superior effect vs. Marcaine at the highest commercially available dose. **p < 0.001 vs. vehicle; ^#p < 0.01 vs. 300 mg/animal Exparel.
Abbreviation: AUC, area under the curve.

Table 3 The activity of local analgesics in SMI and SI incision models in pigs

SMI				SI
Treatment	Study no.	Baseline	3 h post dosing	Treatment	Study no.	Baseline	3 h post dosing
Vehicle	Study 1	55.75±3.16	2.55±0.71	Vehicle	Study 4	60.00±0.00	2.25±0.67
	Study 2	57.38±2.49	3.95±1.52		Study 5	54.33±3.78	3.33±0.33
	Study 3	60.00±0.00	2.00±0.98		Study 6	60.00±0.00	2.85±0.22
Exparel 300 mg/animal	Study 1	53.82±4.28	27.73±5.67**	Exparel 300 mg/animal	Study 4	55.6±5.67	27.00±3.48**
	Study 2	54.96±6.80	27.35±3.16**		Study 5	60.00±0.00	29.10±4.02**
	Study 3	60.00±0.00	26.00±2.49**		Study 6	60.00±0.00	28.36±5.13**
Marcaine 30 mg/animal	Study 1	60.00±0.00	20.20±2.92**	Marcaine 30 mg/animal	Study 4	60.00±0.00	21.33±3.12**
	Study 2	60.00±0.00	18.90±4.86**		Study 5	55.75±6.77	22.6±2.96**
	Study 3	57.38±5.42	23.20±3.2**		Study 6	56.22±5.67	24.65±3.2**
				Ropivacaine 50 mg/animal	Study 4	60.00±0.00	31.20±4.02**
					Study 5	60.00±0.00	38.20±7.12**
					Study 6	54.82±7.12	30.10±3.9**

Notes: Data show the results of three different studies and the activity of the different treatments at the peak of activity at 3 h post dosing.

** p<0.01 vs. vehicle group of the same study. Data are presented as mean ± standard deviation.

Abbreviations: SI, skin incision; SMI, skin and muscle incision.

Figure 3 Withdrawal force following treatment with Naropin (ropivacaine solution), Marcaine (bupivacaine solution) and Exparel (bupivacaine liposomal formulation) in an SI model in the pig.

Notes: The duration of activity of Naropin and Exparel was longer than that of Marcaine. *p<0.05; **p<0.001 vs. vehicle.
Abbreviation: SI, skin incision.