Pharmaceutical Roadshow Flashcards
How does a drug drug interaction show on a graph
Two lines are apart so you must adjust the dose or avoid if there is a safety concern
What is the victim
CYP P-450 substrate
What is an aggressor
CYP P-450 inducer/inhibitor
CYP P-450 induces do what
Speed up drug metabolism so plasma levels decrease
CYP P-450 inhibitors do what
Slowdown drug metabolism so plasma levels increase
When consider risks and benefits of medication you must consider
Disease, alternative treatment, patients preference, evidence, informed consent, patient (genes, family history, lifestyle etc), potential to Give a test dose and increase, case of managing side-effects, compliance
What does generics do
Promote drug innovation, protect/information so company can make money
Generics laws
Data exclusivity for eight years after license, market exclusivity for two years after data exclusivity, patent for 20 years for molecule or formulation
What is nonbiological generic
They do not need to repeat nonclinical and clinical studies but need to show PK bioequivalence
PK bioequivalence values
90% confidence interval within 80 to 125%
Biological generic must show
Efficacy in safety in phase 3 in most sensitive patience
Don’t continue drug/ research if
PK concerns, those care response is U shaped in animal studies, polymorphism of targets, evidence of toxicity, of target affects, effects in human but not seen in animals so non-clinical data not appropriate – change animal subject
Drugs must be developed for use in
Paediatrics as well unless they have a waiver
What is the null hypothesis
Treatments are equal- you would reject the null hypothesis if your drug is more effective
Informed consent in drug development
Provide patient information sheet, involve ethics committee
In drug development you must report all
Side-effects, unexpected efficacy, pregnancy prescribing and breastfeeding prescribing, overdoses/misuse, medication errors, withdrawal symptoms
Major drug therapy achievements
Type one diabetes was a killer before insulin, antibiotics, vaccines e.g. smallpox, heart disease decreased, two out of three people with cancer survived 5+ years, antivirals e.g. HIV and Hepatitis C (chronic/curable)
Many drugs won’t recoup their
Investment even if they make it to market
What is the cost to develop a drug
In 2000 it was $403 million, in 2016 it was $1395 million
Drug development stages
Find potential new target medicine, nonclinical studies, phase 1 clinical studies, phase 2 clinical studies, phase 3 clinical studies, regulatory submission and pricing, launch a new medicine, post-launch R&D, patent expiry and genetic entry
What are the discovery and development phases that take 10 to 15 years
Find potential new target medicine, non-clinical studies, phase 1 clinical studies, phase 2 clinical studies, phase 3 clinical studies and regulatory submission and pricing
What is the launch stages which takes 5 to 10 years
Launch a new medicine and post-launch R&D
How long is patent expiry and genetic entry for
20 years
What happens if there is a food drug interaction
Suggest taking the medicine with no food e.g. four hours after eatint
On a graph how can you tell if there is a food drug interaction
The fed and fasted Lines on the drug plasma concentration are not close to each other
What are the non-clinical testing requirements
Two species toxicology – one rodent and one non-rodent, 14 day exposure for two week use in humans, ideally by the same route e.g. IV, histological examinations of all major organs, PK to say no adverse side-effects and ADME, Check local tolerance, phototoxicity, immuno toxicity and genotoxicity
Non-clinical testing during clinical development
Long-term mammalian studies, reproductive toxicity studies, specific studies on safety findings in humans, carcogenicity studies
Phase 1 trials
Test safety and tolerability using labs, ECG, vitals and monitoring adverse side-effects
Look at PharmaKinetics eg cmax, tmax and t1/2 and oharmodynamics
Look at special populations e.g. with kidneys/liver impairment
Therapeutic dose guide
Drug drug and drug-food interactions
Usually use healthy patients except for cancer drugs

What do you consider when choosing your trial population
Age, gender, other medication and disease, lifestyle and genetics
Things to consider with your trial design
Parallel verse crossover groups, single/multiple doses, starting dose and escalate slowly, use a placebo group/control group, endpoints, location– needs 24/7 emergency cover and staff
Phase 2
Randomised clinical trial, uses patients, enables dose selection, check safety/tolerability/PK/efficacious dose
Phase 3
Registration
2 randomise controlled trials, International data monitoring, uses patients, endpoints – regulatory acceptance, safety essential and patient reported outcomes and needs to be approved by MHRA which can take up to 210 days
Phase 3B
Further scientific data is collected for efficacy and safety, it uses real world evidence
