Safety evaluation of a recombinant plasmin derivative lacking kringles 2-5 and rt-PA in a rat model of transient ischemic stroke

Table 1 Experimental groups and dosing characteristics

Group	n	Dose (mg/kg)	Test Article Concentration (mg/mL)	Injection Volume	Infusion Duration
(Test Article)				(μL/g BW*)
Saline	6	Dose Vol	---	1	10 min
Vehicle	6	Dose Vol	---	1
rt-PA	5	10	5^†	2	20 min
	6	30	5^†	6	60 min
Δ(K2-K5) Plasmin	6	0.15	0.3^‡	0.5	10 min
	6	0.5	0.5	1
	6	1.5	1.5	1
	5	5	5	1

* BW is the body weight. ^† this solution was hyperosmotic (792 mOsmol/L). Solutions of higher concentrations and thus higher osmolality may have significant physiological effects in ischemic brain tissue. ^‡ lower concentrations of Δ(K2-K5) plasmin may have compromised the integrity of the molecule. The total volumes infused averaged 0.35 mL, 0.7 mL and 1.95 mL for infusion durations of 10, 20 and 60 minutes, respectively.

ISSN: 2040-7378