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The Safety Pharmacology Studies Of Hr0905, Prasugrel And Prasugrel Hydrochloride; Telemetry System Qualification

Posted on:2012-03-18Degree:MasterType:Thesis
Country:ChinaCandidate:A P CheFull Text:PDF
GTID:2154330335459123Subject:Health Toxicology
Abstract/Summary:PDF Full Text Request
Objective: To study the effects of HR0905 on the nervous system of mice and cardiovascular and respiratory system of Beagle dogs. Methods: The experimental mice and Beagle dogs were randomly divided into high, medium and low dose groups and a vehicle group which received a single dose of 30, 100, 300 and 0 mg/kg of HR0905 by intragastric (ig) administration respectively and the spontaneous activities and pull-down ability of the animals were observed. The Beagle dogs were also randomly divided into high, medium and low dose groups and control group which received a single dose of 2, 6, 20, and 0 mg/kg HR0905 by ig adminstration respectively and the blood pressure, electrocardiogram(ECG), respiratory rate and rhythm of Beagle dogs were measured. Results: Compared with the vehicle control group, the pole climbing ability of the high dose group of mice decreased significantly after a single ig adminstration of HR0905. Then a downward trend of spontaneous activity was observed in the mice 1.5 h after the administration, and the peak value was detected at 3.5 h. After a single ig administration of HR0905, the heart rate of beagle dogs decreased significantly. The systolic blood pressure, diastolic blood pressure and mean arterial pressure of dogs decreased 2.0 h after administration in the medium and high dose groups, and the peak vale was detected at 4.0 h after administraion. HR0905 had no significant effect on P-wave voltage, T wave voltage, QRS interval, PR interval, QT interval, ST segment of ECG of beagle dogs. HR0905 had no significant effect on respiratory frequency, amplitude and rhythm in Beagle dogs. Conclusion: HR0905 had certain effects on the cardiovascular and nervous systems. The compound could decrease the heart rate of the dogs. There was a downward trend in systolic blood pressure, diastolic blood pressure and mean arterial pressure of beagle dogs. The pole climbing ability of mice decreased significantly and spontaneous activity experienced a downward trend. Objective: To study the effects of prasugrel and prasugrel hydrochloride on the nervous system of mice, the cardiovascular and respiratory systems of Beagle dogs. Methods: The mice were divided into experimental groups and a vehicle control group. The experimental mice received prasugrel and prasugrel hydrochloride by ig administration, which were further divided into low, medium and high dose groups respectively (25,50,100 mg/kg). The vehicle control group received a single dose of 0.5 % CMC-Na solution. The spontaneous activity and ability of the climbing pole of animals were measured. The Beagle dogs were also divided into low,medium and high dose groups which received a single dose of 2.5,5.0,10.0 mg/kg rasugrel and prasugrel hydrochloride by ig administration respectively, and a vehicle control group which received a single dose of 0.5 % CMC-Na solution by ig administration. The systolic blood pressure, diastolic pressure, mean arterial pressure, heart rate, heart rhythm, P-wave voltage, T wave voltage, QRS interval, PR interval, QT interval, ST segment and respiratory rate of ECG of Beagle dogs were measured. Results: Prasugrel and prasugrel hydrochloride had no significant effect on pole climbing ability and spontaneous activity of mice. Prasugrel and prasugrel hydrochloride had no significant effect on systolic pressure, diastolic pressure, mean arterial pressure, heart rate, ECG of the P wave voltage, T wave voltage, QRS time , PR interval, QT interval, ST segment and respiratory rate of Beagle dogs. Conclusion: Prasugrel and prasugrel hydrochloride by a single dose of 25, 50, 100 mg/kg had no significant effect on the nervous system of mice. Prasugrel and prasugrel hydrochloride of a single dose of 2.5, 5.0, 10.0 mg/kg by ig administration had no significant effect on the cardiovascular and respiratory systems of Beagle dogs. Objective: To verify the installation standards, operation standards and performance standards of PA-D70 telemetry system provided by Data Science International (DSI). Methods:According to the requirements of Ponemah Physiology Platform (P3) of PA-D70 telemetry system, the installation qualification was used to verify the P3 system and the analysis module of P3. Under the guidance of manufacturers, users gradually learned and mastered the operation of the equipment and all it's related software, and then completed the operation qualification of hardware and software of the telemetry system. More over, the correlationship of blood pressure values were compared between the PA-D70 telemetry system and the BL-420E+ biological and functional experimental system. During the performance qualification, four Beagle dogs were inserted with inplants and divided into blank group (deionized water), low dose, middle dose and high dose groups to receive 4×4 Latin square of captopril by 16, 32, 48 mg/kg by oral administration respectively. The medication was readministrated after an elution period of three days. To confirm whether the telemetry system could meet the basic requirements of users, observations were conducted on the changes of systolic blood pressure, diastolic pressure, mean arterial pressure, heart rate, ECG indicators of conscious Beagle dogs before administration and at 10 min, 20 min, 30 min, 1 h, 1.5 h, 4 h, 8 h, 12 h, 16 h, 20 h, 24 h after administration. Results: The installation and operation of hardware and software of the telemetry system were successfully verified for the requirements. Using the PA-D70 telemetry system and BL-420E+ biological and functional experimental implant telemetry sub-system, synchronous changes of blood pressure values were observed and the data had a high correlation. Following oral administration of 16, 32, 48 mg/kg of captopril separately in Beagle dogs, descent tendency was observed on systolic pressure, diastolic pressure and mean arterial pressure (10 min ~ 4 h), heart rate ( 20 ~ 30 min) and respiratory rate (30 min ~ 1 h). No drug related significant differences were observed on index changes of ECG. Conclusion: The results of installation qualification, operation qualification and performance qualification showed that the PA-D70 large animal telemetry system was verified to fulfill the basic standard requirements.
Keywords/Search Tags:HR0905, safety pharmacology, cardiovascular system, respiratory system, nervous system, prasugrel, prasugrel hydrochloride, safty pharmacology, telemetry, installation qualification, operation qualification, performance qualification
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