Byrn Lecture 2 Flashcards
Challenges of Drug Development
Short time line (such as pandemics)
Broad Dose Range (warfarin has low dose range)
Minimal Amounts of API
Strategies to these Challenges
Knowledge-based decision making
Prepare in small scale
Determine performance often
Plan for manufacture
Methods of Drug Discovery
Screening
Molecular Modification of known agents
Big Questions that need Answered
What is structure of compound?
What is the likely dose?
What is the route of administration?
What is indication?
How difficult to make?
How soluble is compound?
How well is it absorbed?
What is the toxicology?
Beta Blocker Modification
Dicholorisoproterenol (1958) –> Pronethalol (1962) –> Propranolol (1964)
Process is called drug design by modifying and altering preexisting drugs
Initial Formulation
can begin with a powder
tested only on 10 patients
must be reproducible and knowledgeable
Investigational New Drug Application
- application to get approval from the government
- FDA approves the trial and will then approve
- contains clinical study controls and designs
New Drug Application
- if drug is safe and effective, the company submits a NDA as a formal request to FDA to approve for marketing
NDA Content
- drug product labeling
- FDA review
- Phase 4 studies
- Postmarketing surveillance
- Annual reports
Abbreviated New Drug Application
generic drug application
Biologics License Application
vaccines and antibody application
ADME
Absorption
Distribution
Metabolism
Excretion
Acute Toxicity Studies
give the drug directly to animal to test toxicity
Subacute Studies
fractions of dosages to volunteers to examine toxicity and effects
Pharmacology
science concerned with drugs, their sources, appearance, chemistry, actions, and uses
Preformulation Studies
physical and chemical studies to understand properties of drugs
Partition Coefficient
drug must pass the biological membrane of the lipid or protein
understands the lipophilic:hydrophilic distribution
Drug Solubility
- necessary for absorption and transport
- must contain at least 10mg/ml to provide a minimal response
- can be altered by structure or particle size
Dissolution Rate
- speed or rate at which a substance dissolves
- In 1 to 2 days, the drug will go out through the feces
Physical Form
- crystalline vs amorphous vs liquids
- account for the particle size in determining solubility
Stability
- must have drugs that don’t degrade through time, radiation, altitude
- stay whole through different hydrolysis and heat
Clinical Protocol
ensures the appropriate design and conduct of the investigation
Phase 1 of Clinical Trial
- 1st in human
- determine pharmacology of drug, SAR relationship, side effects of dose increases
PURPOSE: mainly safety
Phase 2 of Clinical Trial
- clinical study of effectiveness in patients with the condition
- dosage selection is made
PURPOSE: effectiveness
Phase 3 of Clinical Trial
- testing on several 100 controlled and uncontrolled trials
PURPOSE: all things considered
Crossover in Trials
A: assigned drug
B: assigned placebo
After a month, it is switched and compared
Annual Reports of Drugs
- must be completed for each approved drug
- annual summary of the significant new information (safety, effectiveness, labeling)
Abbreviated New Drug Application
- nonclinical laboratory studies and clinical investigations may be omitted
- must still contain studies pertaining to drug’s bioavailability and generic drug products
