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1. Introduction
2. Toxicology and safety pharmacology studies
3. Why is safety pharmacology important?
4. ICH guidelines
5. Scope of the S7A guidance
6. ICH topic S7A - safety pharmacology
7. The "core battery" of studies
8. Follow up and supplemental studies
9. Core battery - CNS
10. Follow-up assays (CNS)
11. Core battery - respiratory system
12. Rodent plethysmography
13. Core battery - cardiovascular system
14. Telemeter cardiovascular signals - example
15. QT interval prolongation
16. A normal ECG and torsades de pointes (TdP)
17. QT interval
18. Individual cardiac action potentials and ECG
19. Ionic basis of the cardiac action potential
20. Action potential with IKr blockade
21. In vitro IKr assay
22. What is IKr?
23. Significance of IKr (hERG) blockade
24. In vivo QT assay
25. Measurements to be made and reported
26. "Rate correction" of QT (1)
27. ICH comments on rate correction
28. "Rate correction" of QT (2)
29. Safety pharmacology studies with biologicals
30. What about biologicals?
31. Biologicals - the hERG assay
32. Safety pharmacology endpoint in tox studies
33. Regulatory significance
34. CNS pharmacology in tox studies
35. Respiratory pharmacology in tox studies
36. Cardiovascular system in nonrodent tox studies
37. Digital ECGs from a canine tox study
38. ECG collection from nonhuman primates
39. A solution to the problem
40. Comparison of ECG effects in nonhuman primates
41. Jacketed telemetry components
42. Primate toxicology ECGs via bluetooth telemetry
43. Resting heart rate comparison
44. What about blood pressure?
45. Sphygmomanometry
46. High definition oscillometry (1)
47. High definition oscillometry (2)
48. Direct BP measurement in tox studies (1)
49. Implantation of a miniature BP telemetry device
50. Tracings from 2 nonhuman primates
51. Direct BP measurement in tox studies (2)
52. Conclusion

Topics Covered

• Adverse functional effects of drugs on vital organ systems have resulted in patient deaths and several product withdrawals over the past two decades
• The potential for these effects was not detected in the traditional toxicology studies that were conducted at the time
• These unfortunate events have led to the introduction of new international regulatory guidelines and the creation of a new discipline, known as safety pharmacology, which is distinct from toxicology
• Safety pharmacology involves experts in pharmacology who specialize in acute adverse effects of potential human drugs, primarily on the cardiovascular, respiratory and central nervous system
• These three organ systems have been deemed to be the ones that are acutely critical for life
• If safety pharmacology studies had been conducted in the past, according to today's standards, the vast majority of the drugs that resulted in human deaths would never have made it into clinical development, much less therapeutic usage in patients

Links

Series:

• Non-Clinical Testing for Toxicity of Pharmaceuticals

Categories:

• Pharmaceutical Sciences

Talk Citation

Sarazan, R.D. (2009, July 30). Safety pharmacology in human pharmaceutical development [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/ZCDT9765.
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Publication History

• Published on July 30, 2009

Financial Disclosures

• Dr. R. Dusty Sarazan has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.