Lecture 36 Flashcards
Investigational new drug application
an application to begin administering a drug to human subjects
New drug application
An application to receive approval to market a new drug
NOAEL
highest dose of an agent that does not produce an adverse effect
Accessibility
FDA evaluates benefits/risks for the population
main one we are looking at
Applicability
PROVIDER evaluates benefits/risks for a patient
Acceptability
PATIENT evaluates benefits/risks in terms of personal values
State the three elements of information needed for application of an
Investigational New Drug with the Food and Drug Administration
- animal pharmacology and toxicology
- manufacturing information
- clinical protocol and investigator information
What is the goal of preclinical studies?
Limit the risk to humans in the administration of a new investigational agent
Acute preclinical studies
effect of a single dose in at least 2 species
Repeated dose studies
length depends on anticipated therapy atleast 2 species
Genetic toxicity
determine likelihood cmpd is mutagenic or carcinogenic
Reproductive toxicity
needs depend on target population
multiple species
Carcinogenicity
only for cmpds used in chronic or recurring conditions
NOAEL vs. MABEL
NOAEL is the highest dose of an agent that does not produce a toxic effect
MABEL therapeutic window is so large that it never gets a dose with that toxicity
- justify based on pharmacology
- adjust for anticipated exposure in man
- include anticipated duration of effect
- adjust for interspecies differences in affinity/potency
How do you predict the first dose in man for a new drug?
Step 1: determine NOAEL in animal species
Step2: calculate HED from species
Step 3: determine safety factor (10)
Step 4: divide HED by safety factor to determine MRSD
