Kruse Clinical Trials DSA Flashcards
lead compound
chemical compound that has pharmacological or biological activity and whose chemical structure is used as a starting pt for chemical modification in order to imporve potency, selectivity, or PK parameters
preclinical in vitro and in vivo studies are performed to evaluate what
safety and toxicity profiles
goals of preclincial studies
identify potential human toxicites without human testing
design tests to further define the toxic mechanisms
predict the specific and most relevant toxicities to be monitored in clinical trials
in vitro studies
study factors involved in drugs actions (protein binding and pathways it effects)
establish direct drug target or effects at molecular and cellular levels
test in relevant cell lines
in vivo (animal testing)
effect of organs on healthy first then disease state animals
drug induced effects in animals can’t be guarenteed to be reproduced in humans
all organ systems studied, and metabolic profile of drug ID’d
If pharm properties are safe and adequate and IF compound produces expected results, lead compuond may be submitted for approval to test in humans
no effect dose
max dose at which a specified toxic effect is not seen
lower than threshold of harmful effect
minimum lethal dose
smallest dose that is observed to kill any experimental animal under defined set of conditions
median lethal dose
dose that kills approximately 50% of animals
limitations of preclinical testing
time and cost
number of animals used which is expensive
extrapolation of values (effects on animals may not translate to humans)
rare and adverse events that occur in humans unlikely to be detected in preclinical testing
investigational new drug
drug must be subject of an approved marketing app before distributed across state lines
during trials drugs must be transported across state lines
submission of IND is trying to get permission from FDA to proceed with drug dist
commercial and non-commercial research categories
-each IND must contain preclinical data, manufacturing info, clinical protocls, and investigator info
IRB
protect rights, safety and welfare of humans participating as subjects in research
- can approve, req modifications or disapprove research
- also called IEC and ERB
phase 0 trials
subpharmacological doses of prospective drug candidates administered to human volunteers
- early PK data
- financially adventagious bc cost is low
- good alt when preclinical trials are unreliable
phase I trials
- 25-50 volunteers
- first stage of drug testing in humans
- safe clinical dosage range
- usually not blinded
- absorption, half life and metabolism reported
- in patient
phase II trials
100-200 subjects
- drug efficacy
- placebo, established activre drug for + control and active investigational agent
- efficacy, dosing, toxicities detected and recorded
- clinical centers like hospitals
- drug failure usually occurs here with toxic effects or not efficacious
phase III trials
further establish drug safety and efficacy or large group of pts (300-3,000)
-people with target disease included
cross over double blind design technique
- overall benefit-risk
- most expensive
