Art of Drug Development Flashcards
(13 cards)
Drug -
medicine or other substance (other than food) which has a physiological effect when introduced into the body
Medicine/Pharmaceutical drug used to:
treat
cure
prevent
diagnose a disease
promote well-being
Considerations in the Drug Discovery Process
ADMET:
Drug must be able to be absorbed into the body (A)
Drug must be distributed to the right target (D)
We must know how the drug is metabolized (M)
We must know how the drug gets excreted (E)
We must understand the toxicities of the drug (T)
Drug chemistry - Organic synthesis involves:
- Conversion of little molecules into bigger molecules
- Synthesis of “synthetic” products from natural products (e.g. plant extracts)
- Modification of existing structures
Main routes of drug administration: (9)
- intravenous
- intramuscular
- topical => local effect
- inhalation => rapid & targeted
- oral => portal circulation => liver => first-pass metabolism
- rectal => 50% first-pass
- sublingual => rapid, no first-pass
- intrathecal => CSF
- transdermal => sustained effect
drug discovery process:
- Target selection
- Lead discovery
- Medical chemistry
- In-vitro studies
- In-vivo studies
- Clinical trials & therapeutics
Drug development steps:
- research - process behind a disease => identification of treatments => find molecule that acts on this target [10000 => 10-20]
- confirm effectiveness & safety of these molecules (computerized models, cells, animals) => approval [10-20 => 5-10]
- clinical trials
Clinical trials Phase 1
Safety and pharmacology of a candidate drug will be tested first in:
- small group (20-100) of healthy volunteers
- small doses will be administered
- close supervision
At least half of compounds will usually be considered safe enough to progress to phase 2 trials
Clinical trials Phase 2
Examination of the efficacy of a compound in volunteer patients who have the condition the drug is intended to treat
To avoid unnecessarily exposing a volunteer to a potentially harmful substance:
- use of the fewest number of patients possible to provide sufficient statistical power to determine efficacy (100–500)
- continuous monitoring and assessment
Most drugs that fail during clinical trials do so at Phase 2 because they turn out to be ineffective, have safety problems or intolerable side effects
Aim of Phase 2 studies is to (4)
- determine the most effective dose
- determine the method of delivery (e.g. oral or IV?)
- determine the appropriate dosing interval
- reconfirm product safety
Clinical trials Phase 3
Much larger population of patients (1000-5000, across multiple international sites)
Aim of Phase 3 trials is to
- reconfirm the Phase 2 findings in a larger population
- identify the best dosage regimen
Clinical trials Phase 4
Clinical trials may continue after the release of the new drug in the market
Regulatory authorities may insist on Phase 4 trials for postmarketing safety surveillance (pharmacovigilance) or they may be undertaken by the company to enable them to target distinct markets
