ADMET Flashcards
Def of ADMET:
principle that modern drug development is based on
What are the two main red flags?
- high protein binding
- HERG
Characteristics of high protein binding:
- occurs with lipophilic drugs
- log-p > 2.5 or 3
- > 80% protein binding
Coumadin has what kind of red flag?
- high protein binding (95%)
- log-p = 2.7
Characteristics of HERG:
- codes for rectifying cardiac K+ channel
- helps heart beat steadily
Mutation of HERG leads to…
- easily opened channels and hyper excitability
- drugs can mimic this
- leads to prolonged QT interval
Characteristics of absorption:
- drug should have log between 2-3 and uncharged
- more polar/lipophilic = less absorbed
Characteristics of distribution:
- polarity affects it the most
- non-polar goes to fat
- more lipophilic w/out charge = more protein bound and sent to fat
How do non-polar drugs go to fat?
binds to protein and carries through bloodstream on albumin
Characteristics of metabolism:
- liver detoxifies
- double edged sword
Why is metabolism a double edged sword?
- slow = drug stays around longer
- fast = elimination of drug occurs
What is the pharmacodynamic effect?
drug in target tissues leads to longer effects
- not in circulation anymore though
What is added to enaloprilate to improve absorption?
ester
Examples of some drugs that are activated via metabolism:
- cozaar
- tamoxifen
Highly water soluble drugs are eliminated via…
urine
