Chapter 2: Drug Discovery, Design, and Development

2.1 Drug Discovery

Total time to bring a drug to market: 12-15 yrs
Average cost: $600-800 million
Successful hits: 10 out of 10,000 make it to animal studies, 1 out of those 10 work in
human clinical trials (get FDA approved)
Process
o Phase I: safety and tolerability (dosage levels, side effects) in 20-100 healthy
volunteers (few months to 18 months)
o Phase II: drug effectiveness and safety in a few hundred diseased patients (1-3
yrs)
o Phase III: drug efficacy in several thousand diseased patients, long-term side
effects determined (2-6 yrs)
o New Drug Application (NDA) submitted to FDA (months to years for approval)
o Phase IV: post market drug efficacy and side effect testing

Most drugs are not discovered but are obtained from lead compounds.
Lead compounds: desired pharmacological activity but also undesirable properties
o What undesirable properties? Toxicity, other biological activities, poorly
absorbed orally, poor water solubility, too quickly metabolized
Lead compound modified to make drug candidate (animal testing), further modified to
clinical drug (goes to Phase I)

2.1A Drug Discovery without a Lead

Penicillin
o Discovered by Sir Alexander Fleming in 1928
o Produced in useful form by Sir Howard Florey in 1940
o WWII blocked further investigation of penicillin to keep Germans from access to
it.
o Also, sulfa drugs were already available as antibacterial agents since 1935.