The Comparison Of Characteristics Of Circulatory System Functions Between Con Scious Bama Minipigs And Cynomolgus Monkeys

Objective: To compare the characters of cardiovascular system functions between conscious Bama minipigs and cynomolgus monkeys and the potential advantages in drug development.Methods: ECG,blood pressure and body temperature of conscious Bama minipigs and Cynomolgus monkeys implanted with telemetry transmitters were recorded by telemetry system for 24 hours,and the circadian rhythms were compared.150,300,and 600 mg/kg Erythromycin and 7.5,15,and 30 mg/kg Propranolol were administered to animals in order to evaluate the reaction to drugs.Results: The systolic blood pressure of conscious minipigs is in the range of 120-145 mmHg,diastolic blood pressure is in the range of 77-95 mmHg,and the mean blood pressure is in the range of 91-111 mmHg.Heart rate is in the range of 85-115 beats/min.The systolic blood pressure,and mean blood pressure of cynomolgus monkeys are in the range of 96-111 mmHg and 69-88 mmHg.Heart rate of cynomolgus monkeys are in the range of 116-164 beats/min.The blood pressure of Bama minipigs was higher than cynomolgus monkeys,while the heart rate was slower.Circadian rhythm caused less fluctuation in the physiological parameters in Bama minipigs than in cynomolgus monkeys.A tiny increasing tendency was observed in heart rate in Bama minipigs in night while the heart rates of cynomolgus monkeys decreased in night.QTc intervals in Bama minipigs were more stable than in cynomolgus monkeys which suggested that Bama minipig is a better model for pharmacodynamics study.For the QT intervals correction,individual covariance is the best choice for both Bama minipigs and cynomolgus monkeys.In Bama minipigs,QTcB and QTcF formulation got similar results while QTcB worked better than QTcF in cynomolgus monkeys.At 8 hours at the dosage of 300 mg/kg,and 2,6,8 hours at the dosage of 600 mg/kg after administered Erythromycin by oral gavage to minipigs,QTcB interval significantly prolonged(P < 0.05)and no statistical differences were found after dosing at the dosage of 150 mg/kg compared with vehicle.At 4.5 hours at the dosage of 150 mg/kg,and 2 to 6 hours at the dosage of 300 mg/kg,and 1 to 6 hours at the dosage of 600 mg/kg after administered Erythromycin by oral gavage to cynomolgus monkeys,QTcB interval significantly prolonged(P<0.05).A significant decreasing tendency was observed in systolic blood pressure,and mean blood pressure at 3 and 4 hours after 30 mg/kg Propranolol(P?0.05),and a significant decreasing tendency was observed in systolic blood pressure,diastolic blood pressure,and mean blood pressure at 5 hours after 15 and 30 mg/kg Propranolol(P<0.05).Conclusion: With the low fluctuatioin in physiology parameters and strong anti-interference capability,Bama minipig is an ideal animal model for evaluation of cardiovascular system functions in drug development.The monkey is small and easy to operate,as a standard model for cardiac safety evaluation,for which there is a large historical database,and has a small individual variation to drugs.