Summary
Samenvatting Les 5 'Pharmacokinetics in drug research'
- Course
- Institution
This document includes the summary of Lesson 5 (info slides with notes) of the “Preclinical drug research” course.
[Show more]
Seller
Follow
evagoormans
Content preview
Lecture 5: 9/10Pharmacokine,cs in drug discovery
Introduc)on
- One of the major reasons of drug a2ri4on
o You will stop for development
- If the compound fails you want to know it fast
o Fail fast, fail cheap
- 50%
o Second one is the lack of efficacy
o On the third place you have toxicology
o Adverse effects in man
o 10% are due adverse effects in the clinical phase
o 5% of the drug failure is because of commercial considera4ons
R&D posi)oning
- PK
o Once you come to your lead finding -> in vitro work
o Once we start with the animal studies you will assess exposure of the animals ->
hopefully these exposures correlate with what you predicted in vitro
- Detailed R&D posi4oning
o Assay to assess certain metabolites
o Assess the absorp4on, distribu4on and excre4ng
o Assess the PK in the clinical situa4on
§ You want to know if you reach the clinical relevant concentra4on
o …
Pharmacokine)cs: some basics
- PK: What is your body doing with the drug?
o Rela4onship between what you take in and the drug concentra4on in the blood/certain
4ssues/milk
§ BreasWeeding: children are exposed to the drug -> for lipophilic compounds it can
be that children are exposed to a higher concentra4on than the mother
o Oral drug -> taken up by the enterocytes -> uptake -> liver -> metabolism -> perifer
blood circula4on -> determining bioavailability
- PD: What is the drug doing with your body?
o Rela4onships between the drug concentra4on-4me profile and therapeu4c and adverse
effects
o What is the drug response? What is the therapeu4cal effect?
Distribu(on
- For some of the compounds depending the target you want that the compound stays in the
circula4on.
o Compound against Altzheimer -> compound should enter the brain
- The VD = volume of distribu4on
o Low VD -> compound will stay in the vessels
o High VD -> will easily disturbed to the issues
, o It is a virtual parameter, it is not real, mathema4cally parameter to determine the other
PK parameters
- Can be influenced with the blood flow
o More perfused vs less perfused
§ More perfused is exposed to more compound
- Protein binding is very important
o Albumin is present in the plasma
o In theory it is only the free drug that has a impact
§ Free drug concentra4on is important -> that’s the one that can interact with the
target
o Compound highly bind to albumin -> not permanent (off and on) => you should be
carefully when you determine your free drug concentra4on
- Ioniza4on will also influence the distribu4on
Elimina(on
- Can be also metabolism of the drug, so also the liver
o Hepa4c clearance, kidney clearance
- Some compound are eliminated by the faeces
- First order process
o Amount of drug eliminated is correlated with serum drug concentra4on
§ Paracetamol -> reach some 4me to reach the steady state concentra4on (to get to
the plasma concentra4on which are stable).
- Kel = elimina4on constant
- The clearance: what will eliminated from the liver/kidney or total
o Kel and Vd will determine this
- Elimina4on half life
o In order to know how much of the drug you need to take in and the frequency
§ Short -> take the drug reglementary
§ Example: 30 min -> drug concentra4on is half of what you have taken in => you
want this as long as possible
§ 4 half lifes => drug will be eliminated for 94%
Steady state
- As successive doses are administered, drug begins to accumulate in the body. With first-order
elimina4on, at a certain point in therapy, the amount of drug administered during a dosing
interval exactly replaces the amount of drug excreted (rate in = rate out).
- When this equilibrium occurs, the peak and trough drug concentra4ons are the same for
each addi4onal dose given
- 4 to 5 half lives to get to the steady state
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller evagoormans. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $8.74. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
74534 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy study notes for 14 years now