- Liver microsomes: They are obtained via ultracentrifugation (pellet) and solved in buffer with
go-factors, the drug compound, and to assess UDT affinity: a second compound is added.
The fraction contains phase I enzymes (especially CYPs- and UDT (UDP-
glucuronysyltransferase, a phase II enzyme).
The affinity for phase I enzymes can be assessed, also the affinity to UDT can be assessed by
adding a second compound.
Advantages:
+: easy to obtain
+: CYPS are completely concentrated (pure) so focus on phase I
+: inhibition studies possible add inhibitor
Disadvantages:
-: specific substrates and inhibitors required
-: contains only phase I enzymes and UGT
-: no induction studies possible
- S9 fraction: Obtained via centrifugation at 9000xg (supernatant).
The fraction contains both phase I and phase II enzymes, but less pure than liver microsomes.
Advantages:
+: more complete view (because both phase I and phase II enzymes present)
+: inhibition studies possible
Disadvantages:
-: no induction studies possible
- Primary hepatocytes: contain the complete cell (whole cell ‘machinery’); contain all enzymes.
Advantages:
+: contain whole cell ‘machinery’: induction studies possible
+: contain all metabolizing enzymes so higher metabolizing capacity qualitative
metabolizing profile
Disadvantages:
-: difficult to obtain
-: requires specific techniques
-: metabolizing capacity of DME’s (drug metabolizing enzymes) decreases rapidly after
cultivation
-: takes more time
- Liver slices: liver slices with all cells present.
Advantages:
+: resemble most closely to the in vivo situation
Disadvantages:
-: difficult to obtain: fresh samples practically not possible
-: levels of DMEs decrease rapidly after cultivation
-: requires specific techniques
- Recombinant enzymes: CYP or UGT: individual enzymes are produced in ER of host cell by
gene expression.
Advantages:
+: affinity for specific enzymes can be assessed like CYP3A4, if high affinity dose should be
increased
Disadvantages:
-: only 1 enzyme at a time
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 charlottegevaerts. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $3.79. You're not tied to anything after your purchase.
