More Biotransformation Flashcards
approach for testing acute toxicity
2 species 2 routes
approach for testing subacute or subchronic toxicity
three doses
two species
2 weeks - 3 months testing
approach for testing chronic toxicity
rodent and nonrodent species for more than 6 months
approach for testing effect of reproductive performance
two species usually 1 rodent and rabbits
approach for testing carcinogenic potential
two years two species
approach for testing mutagenic potential
test effects on genetic stability and mutations in bacteria or mammalian cells in culture
approach for testing investigative toxicology
determine sequence and mechanisms of toxic action, discover genes, proteins, etc
no effect dose
max dose at which toxic effect is not seen
min. lethal dose (LDmin)
small dose that is observed to kill any animal
max lethal dose (LD50)
dose that kills 50% of animals
- subpharmacological doses are given
- minimal preclinical toxicology safety testing
- cheapest
phase 0
- first state of drug testing in humans
- comparing humans vs animal results
- 25-50 people
- volunteer patients if drug is expected significant toxicity
- inpatient clinic at research centers
phase I
- 100-200 pts
- single blind
- includes an inert placebo
- measures efficacy, dosing, toxicities
- done at hospitals affiliated w/ universities
phase II
- 300-3000 pts
- crossover and double blind
- placebo
- measuring overall benefit-risk relationship
phase III
- only after approval to market
- post-marking study
phase IV
