Comarison of Effects on Cardiovascular System with 3 Infusion Techniques in Primates

抄録

Administration of the test article by the infusion route in telemetered conscious monkeys has been becoming more generally selected in safety pharmacology studies. The purpose of this study was to assess the feasibility of performing cardiovascular studies with infusion route with comparison of the heart rate (HR) response among 3 different infusion techniques in 4 male primates. In Method 1, the primates were restrained in the chair and infusion was performed through an i.v. catheter. In Method 2 and 3, infusion was performed in the animal’s home-cage via VAP/portable pump. The only differences between Method 2 and 3 were the presence of the technicians in the room (Method 2: yes, Method 3: no) and the infusion dose commencement (Method 2: manually, Method 3: automatically). To minimize the stress, the animals were acclimated to each infusion system (primate restrained-chair/jacket) prior to dosing. In each method, the animals were dosed with saline for 1 hour at an infusion rate of 5 mL/kg/hr. The lowest HR during the infusion period and the minimum HR changes from predose (~1-to 2 hour prior to dose) to postdose period (~2 hour following the completion of the infusion) were observed when the animals were in the home-cage with the jacket and infusion was initiated automatically without human presence (Method 3). Based on the result from saline infusion, the assessment of QT interval was assessed with Method 3 using sotalol infusion (4 mg/kg/hr) and QT prolongation was observed.