Drug Toxicity and Drug Development Flashcards
Lecture 7
Identify the three levels of risk_benefit analysis that occur related to drug therapy
Accessibility, applicability, and acceptability
State the three elements of information needed for application of an Investigational New Drug with the FDA
Animal pharmacology and toxicology, manufacturing information, clinical protocol and investigator information
Differentiate the No Observable Adverse Effect Level and Minimal Anticipated Biological Effect Level for determining the first dose in man for an investigational drug
NOAEL is derived from toxicology studies. It indicates the highest exposure without causes toxic or harmful effects in animals. The NOAEL is typically translated to a human equivalent dose (HED). Adjust for anticipated exposure in man.
MABEL is the lowest dose expected to produce a minimal biological effect in humans.
Identify the primary reasons adverse drug events are often not detected until
after the drug is approved and marketed for a period of time.
- Rare events vs. patient numbers in clinical trials. Rare adverse reactions are not picked up in clinical trials.
- common events vs. patient numbers and duration in clinical trials
Provided key information about a potential pharmaceutical excipient (such as its
presence on the GRAS list) determine whether or not preclinical toxicology
studies are needed for its inclusion in a dosage form
GRAS has a list of excipients that dont need review if used. Saves time and money
Name the five categories of preclinical studies typically completed in the
development of a new drug.
Acute studies (effect of single dose with at least 2 species), repeated dose studies (length depends on anticipated therapy), genetic toxicity (determine likelihood compound is mutagenic or carcinogenic), reproductive toxicity (needs depends on target population with multiple species), carcinogenicity (only for compounds used in chronic or recurring conditions)
