According to EMA guideline on setting health based exposure limits, to calculate PDE for a specific substance, we have to establish NOEAL or LOEL. However, there is no available data of NOEAL or LOEL for penicillins or cephalosporins, so how can I derive PDE in this case? Can I use LD50 value instead and there is any correlation between PDE and LD50?
Thank you!
No, there's no obvious correlation between PDE and LD50, because NOEAL or LOEL for PDE came from long-term repeated dose toxicity and LD50 from single dose.
I think the idea of PDE does not go well with most of antibiotics, because a PDE for a particular agent is an index of safety for chronic use and most of the antibiotics are not recommended for long term use.
I do know that this would be relevent. I also know that 10 international units of penicillin are enough to cause an allergic reaction. All of these powders are absorbable. We recommend to use a closed system for preparing, adding sterile diluent, and continue to use this closed system all the way to the needless catheter and the patient. I work at the veterinary college, and we have had numerous clinicians become allergic to penicillin from preparing potassium penicillin 20 M. U. vials as well as several horse owners.
Thanks, Sue.
I think it is a good example of chronic exposure and safety of penicillins.
Masaki
Yes, you can use the highest dose studied in the long term toxicity study with the longest dosing duration as NOAEL if there's no toxic finding. However, the allergic toxicity in humans cannot be predicted from animals.
Masaki
I think you should choose a NOAEL value for each animal from a study with the largest exposure and calculate a PDE value for each animal, then use the smallest PDE for the agent.
Masaki
Penicillins or cephalosporins are considered highly sensitizing compounds by the EMA and FDA. Therefore, they will required dedicated facilities for penicillins and non-penicillins beta lactams. With this in mind, you will still need to establish PDEs (aka ADEs) between the different beta lactams to prevent cross-product contamination from one beta lactam to the other. The toxicology experts at Affygility Solutions have established a large number of PDEs for beta lactam compounds. Our catalog can be found here: https://goo.gl/U1GYcR
I should mention that PDE/ADE reports by expert toxicologists are not free. These experts have decades of professional experience and advance degrees from top-ranked schools. They expect to get paid for their work effort.
Dear Hong Doi,
Follow TTC approach.. The Softwares such as Toxtree and QSAR Tool box are useful in deriving the PDE for the compounds which doent not have NOAEL/LOAEL/LOEL/NOEL..
http://toxtree.sourceforge.net/
Hope the information is useful to you.
Regards
G.L.Vishwanath
Dear Masaki Hiraoka as you said
""Yes, you can use the highest dose studied in the long term toxicity study with the longest dosing duration as NOAEL if there's no toxic finding. However, the allergic toxicity in humans cannot be predicted from animals.''
Can you please give references regarding this statement. I need reference for this to use in PDE determination.
Thanks in advance
Scientist, please give me an example of veterinarians that administer 80 M.U. Potassium Penicillin G to a horse IV daily for 7 days. They are also exposed to the urine that is elimninated by the horse. As I mention, I am told by the MD that 10 I.U. can trigger an allergic reaction. We have numerous equine veterinarians that are allergic to penicillin as they mix and administer the drug, and may very well clean the stalls. I have them using a closed system to mix and administer at the clinic after we mix it under USP 797 guidelines, but not being done by private practitioners? Need some references. Thanks Sue
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