We noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Simplified prodrug concept
- Broader space for prodrug design
- Prodrug strategies for common functional groups
- Rationale for prodrug design
- Increased solubility for IV use
- Release of propofol from fospropofol
- Phosphate esters for alcohols and phenols
- You should NOT be concerned about formaldehyde
- Phosph(on)ates for other functional groups
- Other solubilizing promoieties for IV use
- Solubility/dissolution barrier for oral delivery
- Overcoming solubility problems for oral delivery (1)
- Overcoming solubility problems for oral delivery (2)
- Clinical development of fosamprenavir
- Recent phosphate prodrugs for oral delivery
- Novel phosphate prodrug strategy
- Amino acid vs. phosphate esters
- Novel ionized promoiety for increased solubility
- Permeability barrier for oral delivery
- Overcoming poor oral permeability
- Preclinical challenges
- Lipophilic prodrugs for better absorption
- Enzymatic conversion of dabigatran etexilate
- Prodrugs for phosphates & phosphonates (1)
- Prodrugs for phosphates & phosphonates (2)
- Phosphoramidate prodrugs in clinical use
- Sometimes simple strategy works just fine
- Toxicity barrier
- Site-selective release to decrease side-effects (1)
- Site-selective release to decrease side-effects (2)
- Site-selective release to prevent abuse (1)
- Site-selective release to prevent abuse (2)
- Prodrug & parent together to prolong duration of drug action
- Prodrugs are surprisingly common!
- Challenges and considerations
- Take home message
- Further reading
Topics Covered
- Introduction to the prodrug concept
- Prodrugs for improved solubility
- Prodrugs for improved absorption
- Prodrugs for reduced toxicity
- The prevalence of prodrugs
- Challenges using prodrugs
Links
Series:
Categories:
External Links
Talk Citation
Rautio, J. (2022, July 31). Prodrug strategies to overcome problems in drug therapy [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 6, 2024, from https://doi.org/10.69645/NTWS8687.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Jarkko Rautio has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Pharmaceutical Sciences
Transcript
Please wait while the transcript is being prepared...
0:00
Hi, my name is Jarkko Rautio.
I'm a Professor in
Pharmaceutical Chemistry
and Vice Head at the
School of Pharmacy,
University of Eastern Finland.
The focus of this lecture
is on prodrug strategies
to overcome problems
in drug therapy.
0:18
This slide shows you an
outline of the lecture.
The first part will briefly
cover the broad concept
of what prodrugs are and
what prodrugs there are.
This will then lead to
examples of prodrugs that
have been able to overcome
various ADMET issues.
Most of the examples
will be dealing with
prodrugs that were
made to improve
either poor solubility
or poor lipophilicity.
But there'll also be
examples designed to reduce
toxicity issues mainly by
controlling the release
of the active parent drug.
I will then discuss
some prodrug numbers
and recent prodrug approvals.
The final part of the
lecture will shortly
cover preclinical issues
regarding prodrugs,
and things to consider
when working on prodrugs
with a take home message.
Several examples given in
this lecture are described
in an extensive prodrug review
that was published in 2018.
1:17
This is a simplified
prodrug concept.
A drug promoiety
molecule is a prodrug.
According to the definition,
it is pharmacologically
inactive or
significantly less active
than the parent drug.
The barrier which a
prodrug should overcome
can be basically any
biological barrier,
such as an epithelial barrier,
or it can be a
physicochemical barrier,
such as poor solubility
or poor lipophilicity.
Both can result in poor
absorption and so on.
Once the prodrug has
overcome the barrier as an
inactive compound, it
must undergo conversion,
which, in most cases, is
an enzymatic conversion
to release the active
parent drug in the body.