July 11, 2025 • 21 mins
When traditional dewormers fail against resistant hookworms, veterinarians may turn to emodepside as a last resort. But are all formulations created equal? Not according to recently published research.
Join us as Theresa Quintana and Drs. Jeba Jesudoss Chelladurai and Stephanie Martinez reveal critical findings about bioequivalence between different emodepside formulations. Their research demonstrates that the feline topical formulation, when given orally to dogs at 3 mg/kg, produces approximately three times higher peak concentrations and 2.4-2.8 times greater systemic exposure compared to the EU canine modified-release tablet at the same dose.
These findings carry significant clinical implications, particularly for dogs with MDR1 mutations lacking P-glycoprotein transport mechanisms. Without this protective system, emodepside can accumulate in the brain and cause neurotoxicity. The research team guides us through proper diagnostic confirmation of resistant hookworms, recommended treatment approaches, and crucial safety considerations before turning to this last-line therapy.
The conversation expands into formulation differences, bioavailability challenges, and practical clinical protocols. Teresa, Jeba, and Stephanie emphasize that clients must follow strict fasting guidelines before and after administration, as food dramatically enhances emodepside absorption and could potentially lead to toxicity with the already higher-concentration feline product.
Whether you're dealing with suspected resistant hookworms in your practice or simply want to understand the science behind bioequivalence and drug safety, this episode provides essential knowledge for evidence-based clinical decision-making. This episode centers around the intersection of parasitology, pharmacology, and clinical medicine and highlights why the details matter when it comes to drug formulations and routes of administration.
AJVR article: https://doi.org/10.2460/ajvr.25.01.0027
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Greenies (00:00):
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(00:22):
digestion and more, Whether it'smealtime or mobility support
Greenies helps you care for yourdog from the inside out.
Learn more at Greeniescom.
Sarah Wright (00:35):
This is Veterinary Vertex, a podcast of the AVMA
Journals.
In this episode, we chat abouthow topical and oral emodefside
formulations for last-linetreatment of multi and homotic
drug-resistant hookworms, whengiven orally to dogs, are not
bioequivalent with our guestsTheresa and, Jeba Jesudoss
Chelladurai and StephanieMartinez.
Lisa Fortier (00:59):
Welcome listeners.
I'm Editor-in-Chief LisaFourier, and I'm joined by
Associate Editor Sarah Wright,Theresa, Jeba and Stephanie.
Thank you so much for takingtime out to be with us here
today.
Thank you for having us Thanksfor inviting us.
Sarah Wright (01:13):
Yes, all right, let's dive right in.
So, Jeba, your AJVR articleprovides critical
pharmacokinetic data onamodepside in dogs, highlighting
significant differences insystemic exposure between
formulations and routes ofadministration.
Please share with our listenersthe background on this article.
Jeba Jesudoss Chella (01:31):
Emodepside is this new drug class of
antiparasitics that is calledthe octadepsypeptide.
It was first patented in 2001for nematodes of animals.
It is a wholly differentmechanism of action compared to
the other drug class that wehave on the market, so currently
it is available as abroad-spectrum antihelminthic
and it is used for the treatmentof parasitic nematodes in dogs
(01:55):
and cats, especially in Europe,where there are two products
that are available.
It has also recently been usedto treat Onchocerca in humans,
although in the US we only havea cat product that is applied
topically.
So there is a Europeanformulation for dogs, which we
do not have in the US, and thatis where our story begins.
Sarah Wright (02:18):
Yeah, I learned a lot through reading your
manuscripts.
So, Theresa, what are theimportant take-home messages
from this AJVR article?
Stephanie Martinez (02:33):
Yeah.
So, I think formulation androute of administration really
matter.
So, Theresa, what are theimportant take-home messages
from this AJVR article?
Mg per kg.
It led to significantly higherplasma concentrations compared
to that EU canine modifiedrelease tablet at that same dose
, a mg per kg.
So specifically, we saw thatthe Cmax, or peak concentration,
(02:56):
was approximately three timeshigher and the AUC, or the total
systemic exposure, was 2.4 to2.8 times greater.
So this kind of indicates thatthese two formulations are not
bioequivalent.
The title of our article, asdefined by the FDA,
bioequivalence, means that twoproducts are equally
(03:17):
bioavailable, meaning equal inthe rate and extent to which the
active ingredient is absorbedand then becomes available at
the site of the drug action.
So this is really importantbecause bioequivalence is the
standard used by the FDA todetermine whether a generic or
alternative formulation can beexpected to have the same
(03:37):
clinical efficacy and safetyprofile as that original or
reference product you're testingagainst.
So in our case that's the EUmodified release tablet.
So if the do products aren'tbioequivalent, we can't actually
assume that they'll behave thesame or have the same safety
margins.
And then so that brings us tosafety.
(03:59):
So imidexide is aP-glycoprotein or PGP substrate
which is particularly importantfor dogs with NDR1 mutations.
So these dogs lack afunctioning PGP transporter,
which normally keeps certaindrugs out of the brain, and so,
without it, drugs likeemodepside can accumulate and
cause neurotoxicity.
So since we don't have anapproved canine emodepside
(04:22):
product here in the US, anyoff-label use of this feline
topical formulation should beapproached with caution.
Lisa Fortier (04:30):
Yeah, really outstanding points that you
highlighted from your article.
So thank you for that reallyclear take-home message.
Jeba, what sparked yourresearch interest in this topic?
Jeba Jesudoss Chelladurai (04:42):
So we first became interested in
emodebsside because there was astudy published in 2020 by our
parasitology colleagues from theUniversity of Georgia.
In that study, Dr Jimenez-Castroand colleagues were working
with resistant hookworms.
Very specifically, they hadisolated a hookworm from a
greyhound and in control testingin their lab they found that
this hookworm wasmulti-anthelmetic resistant, so
(05:03):
it was resistant to fenbendazole, pyranthopamide and milbimicin
oxime, and the only drug thatworked in their trials was
imodepside.
So imodepside in that study had99.6% efficacy and following
that study they had sort ofwritten this article in
Clinician's Brief that suggestedthat in the case of multiple
(05:25):
anthihelminthic resistance,Imodepcide could be used
potentially to treat dogs thatare infected.
And now the only problem thathas been that we don't know if a
given dog that is brought to aveterinary clinic has hookworms
that are resistant to all thedifferent drug classes that are
available on the market.
And so that's where ourinterest in Imodev site sparked,
(05:48):
because people read thatarticle and they would then go
and purchase this product andgive it extra label.
So they were giving the catproduct, which is meant for
topical use orally to dogs, andreally that's what sparked my
interest, because I wasconcerned about safety in all
these different dogs that werebeing treated this way.
Lisa Fortier (06:12):
Yeah, I can see why that would happen.
Stephanie, we heard fromTheresa some probably surprising
findings, I would think basedon Theresa's expression and her
tone like, ooh, the area underthe curve and the PK and all
those things.
But what did you find the mostsurprising thing from this
article?
Theresa Quintana (06:30):
Well, Truly, I expected that we were going to
find overall higherconcentrations when we gave the
topical feline product orally tothe dogs.
Just because it's solubilized,it has accelerants like alcohols
in it, as opposed to the EUformulation which is modified
(06:52):
release and is going to requiredissolution in order for it to
be solubilized and be absorbed.
I just did not know, or I wassurprised.
I guess that it was aboutthreefold higher concentrations
and I think just the magnitudedifference for me was surprising
.
I was simply just not expectingit.
(07:13):
And then, similarly, when wedid give the topical formulation
topically to the dogs, we hadincredibly low concentrations
and I suspected, just because ofthe physiological differences
between skin for cats and dogs,I suspected it was not going to
be as high, but I did not thinkit would be quite as low as we
found.
(07:33):
So I think just the magnitudewas ultimately the between
routes was quite surprising.
Lisa Fortier (07:40):
Yeah, that actually speaks to safety as
well.
Theresa Quintana (07:42):
Right, Like you know, we often think of
safety as avoiding adverseevents, but if the drug isn't
being delivered and doesn't work, that's a safety issue as well,
and I think it's a really greatreminder for our veterinary
community that, just you know,giving the same drug at the same
dose with differentformulations does not guarantee
(08:03):
the same effect, and I thinkthat's just sometimes we forget,
and so it's a really greatreminder.
Yeah, excellent points.
Sarah Wright (08:10):
I come from the zoo world, where things often
are, you know, extra label usetrying to find indications of
certain species, so always goodinformation to keep in mind.
So, Theresa, what are nextsteps for research in this topic
?
Stephanie Martinez (08:22):
Yeah, great question.
So I think if a canineFDA-approved imidapside product
remains unavailable here in theUS and we continue to rely on
this extra label use of thefeline topical formulation as
just kind of this last linetreatment for these
multi-antelmetic drug-resistanthookworms, then the next
critical step would be toinvestigate whether lower doses
(08:45):
of the feline topical productcan achieve bioequivalence to
the EUK9 product, and thenideally we would pair that with
some clinical efficacy studiesagainst multi-antelmetic
drug-resistant hookworms toensure it's both effective and
safe for use in dogs.
Very cool.
Sarah Wright (09:03):
Now this next question deals with AI, which is
definitely a super interestingtopic in veterinary medicine and
for our listeners.
If you haven't already, youshould definitely read our new
AJVR AI Supplemental IssueArtificial Intelligence in
Veterinary Medicine from Barksto Bytes.
So, Jeba, do you see a role forAI in this area of research?
Jeba Jesudoss Chelladurai (09:22):
So in specifically pharmacokinetic
research, in terms of how we didour study, probably not,
although I would cautionveterinarians and because I
teach vet students, I cautionthem all the time about, you
know, ethical use of AI, butalso making sure that AI is
accurate and what it is sayingwhen it comes to diagnosis and
(09:43):
treatment of our patients,because in some models of AI
they're always not the mostaccurate.
So, especially with extra labeldrug use like this, that's
where my only caution is,especially with extra label drug
use like this.
That's where my only caution is.
But in terms of research, Iknow it's coming.
I unfortunately haven't quiteread your AJVR article yet, but
(10:03):
right now, in thepharmacokinetic aspects of the
research, like we did it, Idon't see a role for AI yet.
Lisa Fortier (10:36):
Yeah, in the journals, what we do.
I update our AI policies forlack of a better word quarterly
because, as Sarah said, it's sorapidly evolving it's hard to
keep up.
But right now I rejected amanuscript.
At least 75% of the referenceswere fake, like completely fake,
so you could tell that theseauthors one.
I'm not sure that the wholemanuscript wasn't faked, but we
have programs that our copyeditors run through everything
(10:57):
to know so they can reformat thereferences and they get flagged
like this isn't real.
So I wrote back to the authorsand I was like rejected flat out
and please don't submit to usagain.
Because even if you did use AIand asked it to generate
references, you should, andasked it to generate references,
you should check them right.
(11:19):
So just be you know, again, ithas a great role.
It's really tricky inscientific writing, and don't
forget, too, anybody who doesupload their information to AI.
You don't know where that goes.
So if you put your researcharticle or your data into AI and
ask it to interpret it, you'vejust lost control of it.
Jeba Jesudoss Chelladurai (11:36):
Right .
A long time ago some IT experttold me if the product is free
to you, then you are the product.
I've always taken that to heart.
Lisa Fortier (11:47):
True Copyright's an issue.
Sarah Wright (11:50):
Yep, nothing's truly free.
And for those of you justjoining us, we're discussing how
topical and oral imodepsideformulations for last-line
treatment of multi-anhylmeticdrug-resistant hookworms, when
given orally to dogs, are notbioequivalent with our guests
Theresa Jeba and Stephanie.
So Jeba, how did your trainingor previous work prepare you to
write this article?
Jeba Jesudoss Chelladurai (12:11):
Yeah, so I'm a veterinarian who
trained in India.
I got my advanced training inveterinary parasitology in the
US and for my PhD I worked ontoxic caracanis, the common dog
ground worm.
I worked on MDR-1, which isalso known as PGP, and my
special interest has been indrug-resistant hookworms.
(12:32):
So when the hookworm resistanceissues came around in 2019 and
2020, I was almost immediatelyinterested.
At the same time, I wasstarting as an assistant
professor at Kansas StateUniversity, so I built my
research program aroundresistance, identifying
knowledge gaps that then I couldfill.
So this was a knowledge gapthat I identified almost
immediately because of safetyissues.
(12:53):
Because of safety issues, one,it triggered my PGP bells
because Imodepside is a PGPsubstrate and in dogs that are
mutant for MDR1, it couldpotentially cause neurological
signs and it will causeneurological signs and so this
kind of tied in my interests inpharmacology, zoonotic nematodes
(13:15):
and then definitely the MDR1piece.
Lisa Fortier (13:19):
Yeah, really great .
We like to ask this question ofeverybody, because veterinary
medicine is such a fabulouscareer and you can go in a lot
of different directions.
So, Stephanie, how about you?
How did your training help youwrite this article?
Theresa Quintana (13:31):
So my PhD training focused on
bioanalytical method development, pharmacokinetics and
regulatory science, which is thefoundation of this work.
And then during my postdoc atthe Program for Individualized
Medicine at Washington StateUniversity's vet school, I
gained a lot of hands-onexperience conducting
pharmacokinetic studies inclient-owned dogs, which helped
(13:52):
us with our recruiting at KansasState.
And then really through myentire career, from
undergraduate until even now asan assistant professor at Utah
State University's brand new vetschool, I've been partnering
with veterinarians to reallytackle clinically relevant
pharmacology questions, whichwas really kind of shaped how
(14:13):
I've approached research likethis.
Lisa Fortier (14:16):
Fantastic Theresa.
How about you Bring it home?
How did your training help youwrite this article?
Stephanie Martinez (14:21):
Yeah, so as Dr Jeba's PhD student I'm kind
of like building on her researchwith PGPs and toxic caricanis.
So that kind of helped me, youknow, understand the
pharmacological and molecularmechanisms behind are relevant
to emidexide.
And then I also have abackground in animal health
regulatory affairs.
(14:41):
So that kind of gave me goodinsight into how formulation,
bioequivalence, drug safety, howthat's all evaluated of the FDA
.
I also have my master's inpublic health and I'm certified
in public health.
So, I think that traininghelped me like kind of
critically assess drug use froma population health and safety
perspective and then kind ofhelped frame that like in a
(15:06):
clinical and regulatoryimplications for off-label use
of imidapside in dogs.
Lisa Fortier (15:11):
Fantastic, what great diversity and approach and
opinion within one problem.
That's awesome.
Sarah Wright (15:18):
Now, this next set of questions is going to be
very important for our listeners, and the first one is going to
deal with the veterinarian'sperspective.
So, jeba, what is one piece ofinformation the veterinarian
should know about?
Emodepside in dogs.
Jeba Jesudoss Chelladurai (15:30):
Okay.
So veterinarians managingsuspected multiple antihelminic
drug resistance cases in hookwebs should not directly jump to
using Imodepside as their firstline of treatment.
First they should first focuson establishing that the dog
that they're dealing withactually has resistant hookworms
using properly timed diagnostictests.
Specifically in this case thatwould be a fecal egg count
(15:52):
reduction test that they canperform or get that test done at
any diagnostic lab that theywork with.
After that they should.
After establishing resistance,they can then use a combination
of Drontal Plus, which hasFabantyl Pyrantyl as the two
actives that are going to workagainst the hookworms, and
topical moxidectin, eitherAdvantage Multi or Equivalent
(16:18):
topical moxidectin, eitherAdvantage Multi or Equivalent,
and then, in case of failurewith that treatment, again
assess through an FECRT.
Then they should reach out forthis VLAN formulation of
Imodevcide.
But that should be the lastline of treatment and while they
do, if they do get to that step, they should exercise caution,
making sure that their patientis not MDR1 mutant.
And if they have an MDR1 mutantdog they should seek other
(16:43):
lines of treatment.
So, amorepside should really beused as a last line of
treatment after making sure thatnothing else works.
In addition, they shouldencourage owners to pick up
after their animals so that theyprevent reinfection, which is
very, very important in dealingwith hookworm cases.
Sarah Wright (17:00):
Yeah, I'm always surprised how many like dog
droppings.
I just see like around.
I'm like this is such a publichealth concern, like pick up
after your pets, please.
It's always wild, but thank youfor providing that decision to
me too.
And on the other side of therelationship, what's one thing
that clients should know aboutthis topic?
Jeba Jesudoss Chelladurai (17:21):
So clients should know about this
topic.
So clients should definitely goto their veterinarians yearly,
take their veterinarian's advice, especially as it relates to
deworming schedules, and reallyread through the instructions
that their veterinarian providesthem or gives them orally,
especially as it pertains toproducts.
So there are some products thatare monthly and they should be
given monthly.
There are some products thatdon't cover hookworms, that are
not monthly, and so in that casethey should consult with their
(17:44):
veterinarians to understandwhich product their pet is on
and, again, as a good owner,they should pick up after their
dogs and dispose of the fecesproperly, because, like I just
mentioned, it is a zoonoticparasite, meaning that hookworm
larvae can penetrate human skinand cause what is known as
cutaneous larval migraines inhumans, and so they should be
(18:07):
aware of that.
Theresa Quintana (18:09):
I might also add and just reiterate what Jeb
has said for owners, which isyou must follow your
veterinarian's written and oralinstructions, especially with
emodepside, and probably themost important thing for an
owner to remember is not to feedyour dog overnight.
So, keep your dog fastedovernight and then do not feed
them for at least four hoursafter administration.
(18:31):
So, emodepside's absorption ismarkedly enhanced with food.
Modepside's absorption ismarkedly enhanced with food, and
so giving the feline topicalformulation off-label, knowing
already that we're getting aboutthreefold higher concentrations
, you can imagine giving thatwith food, we would be really
concerned about toxicity.
So, I think again, justfollowing instructions for
(18:55):
owners, that's very important.
Lisa Fortier (18:56):
I think again, just following instructions for
owners.
That's very important.
Great points, Thank you, guys.
This is very interesting.
Stirs up lots of other ideasfor our journal collections and
other things for the One Healthside of our veterinary
profession.
So as we wind down, we'd liketo ask some fun facts.
So, Jeba, we'll start with you.
What is your favorite animalfact?
Jeba Jesudoss Chelladurai (19:16):
Right .
So thank you for that question.
So my favorite animal fact,which I think is really cute, is
sea otters often hold handswhile they sleep.
This behavior is known asrafting, and because they spend
so much of their time in water,they want to prevent, you know,
floating away while they're atsea.
So they often sleep eitherentangling themselves in kelp
(19:36):
forest or by holding hands, andit's a good way to prevent
drifting away from the group.
That's adorable.
It's cute to see as well.
Lisa Fortier (19:45):
Theresa on a different subject.
When you complete a puzzle, doyou do the border exterior
pieces or do you start with acolor or a theme in the inside?
Stephanie Martinez (19:55):
So I do start with the border exterior
and that's because I need like asatisfying sense of progress
right away to keep going tofinish.
Lisa Fortier (20:05):
Yeah, same with me .
I need some structure to get megoing.
Stephanie, on a differentsubject, what was the first
concert you attended?
Theresa Quintana (20:14):
That's a good question.
I have a very eclectic tasteand this is probably going to
age me, but I went to a Weezerconcert, so a rock band from the
90s.
Sarah Wright (20:30):
But yeah, that's awesome, they're actually coming
back to Chicago in September, Ibelieve.
Theresa Quintana (20:32):
So I was actually looking at going yeah,
it's a great show, they're agreat band, so let's get to here
.
Sarah Wright (20:37):
Thank you, and just thank you all again for
being here today, for submittingyour manuscript to AJVR and for
sharing the findings with ourlisteners.
Theresa Quintana (20:44):
Thank you, yeah, thank you again for having
us, yeah.
Sarah Wright (20:48):
And to our listeners.
You can read Theresa Jeba's andStephanie's article on AJVR.
I'm Sarah Wright with LisaFortier.
Be on the lookout for nextweek's episode and don't forget
to leave us a rating and reviewon Apple Podcasts or whatever
platform you listen to.
From the makers of vet-recommended Greenies dental
treats comes an easy way tosupport your dog's wellness.
Greenies Smart Essentials dryfood delivers complete, balanced
nutrition with science-backedrecipes.
Greenies Supplements, developedby a team of PhD animal
nutritionists, offers options tohelp support healthy joints,
(00:22):
digestion and more, Whether it'smealtime or mobility support
Greenies helps you care for yourdog from the inside out.
Learn more at Greeniescom.
Sarah Wright (00:35):
This is Veterinary Vertex, a podcast of the AVMA
Journals.
In this episode, we chat abouthow topical and oral emodefside
formulations for last-linetreatment of multi and homotic
drug-resistant hookworms, whengiven orally to dogs, are not
bioequivalent with our guestsTheresa and, Jeba Jesudoss
Chelladurai and StephanieMartinez.
Lisa Fortier (00:59):
Welcome listeners.
I'm Editor-in-Chief LisaFourier, and I'm joined by
Associate Editor Sarah Wright,Theresa, Jeba and Stephanie.
Thank you so much for takingtime out to be with us here
today.
Thank you for having us Thanksfor inviting us.
Sarah Wright (01:13):
Yes, all right, let's dive right in.
So, Jeba, your AJVR articleprovides critical
pharmacokinetic data onamodepside in dogs, highlighting
significant differences insystemic exposure between
formulations and routes ofadministration.
Please share with our listenersthe background on this article.
Jeba Jesudoss Chella (01:31):
Emodepside is this new drug class of
antiparasitics that is calledthe octadepsypeptide.
It was first patented in 2001for nematodes of animals.
It is a wholly differentmechanism of action compared to
the other drug class that wehave on the market, so currently
it is available as abroad-spectrum antihelminthic
and it is used for the treatmentof parasitic nematodes in dogs
(01:55):
and cats, especially in Europe,where there are two products
that are available.
It has also recently been usedto treat Onchocerca in humans,
although in the US we only havea cat product that is applied
topically.
So there is a Europeanformulation for dogs, which we
do not have in the US, and thatis where our story begins.
Sarah Wright (02:18):
Yeah, I learned a lot through reading your
manuscripts.
So, Theresa, what are theimportant take-home messages
from this AJVR article?
Stephanie Martinez (02:33):
Yeah.
So, I think formulation androute of administration really
matter.
So, Theresa, what are theimportant take-home messages
from this AJVR article?
Mg per kg.
It led to significantly higherplasma concentrations compared
to that EU canine modifiedrelease tablet at that same dose
, a mg per kg.
So specifically, we saw thatthe Cmax, or peak concentration,
(02:56):
was approximately three timeshigher and the AUC, or the total
systemic exposure, was 2.4 to2.8 times greater.
So this kind of indicates thatthese two formulations are not
bioequivalent.
The title of our article, asdefined by the FDA,
bioequivalence, means that twoproducts are equally
(03:17):
bioavailable, meaning equal inthe rate and extent to which the
active ingredient is absorbedand then becomes available at
the site of the drug action.
So this is really importantbecause bioequivalence is the
standard used by the FDA todetermine whether a generic or
alternative formulation can beexpected to have the same
(03:37):
clinical efficacy and safetyprofile as that original or
reference product you're testingagainst.
So in our case that's the EUmodified release tablet.
So if the do products aren'tbioequivalent, we can't actually
assume that they'll behave thesame or have the same safety
margins.
And then so that brings us tosafety.
(03:59):
So imidexide is aP-glycoprotein or PGP substrate
which is particularly importantfor dogs with NDR1 mutations.
So these dogs lack afunctioning PGP transporter,
which normally keeps certaindrugs out of the brain, and so,
without it, drugs likeemodepside can accumulate and
cause neurotoxicity.
So since we don't have anapproved canine emodepside
(04:22):
product here in the US, anyoff-label use of this feline
topical formulation should beapproached with caution.
Lisa Fortier (04:30):
Yeah, really outstanding points that you
highlighted from your article.
So thank you for that reallyclear take-home message.
Jeba, what sparked yourresearch interest in this topic?
Jeba Jesudoss Chelladurai (04:42):
So we first became interested in
emodebsside because there was astudy published in 2020 by our
parasitology colleagues from theUniversity of Georgia.
In that study, Dr Jimenez-Castroand colleagues were working
with resistant hookworms.
Very specifically, they hadisolated a hookworm from a
greyhound and in control testingin their lab they found that
this hookworm wasmulti-anthelmetic resistant, so
(05:03):
it was resistant to fenbendazole, pyranthopamide and milbimicin
oxime, and the only drug thatworked in their trials was
imodepside.
So imodepside in that study had99.6% efficacy and following
that study they had sort ofwritten this article in
Clinician's Brief that suggestedthat in the case of multiple
(05:25):
anthihelminthic resistance,Imodepcide could be used
potentially to treat dogs thatare infected.
And now the only problem thathas been that we don't know if a
given dog that is brought to aveterinary clinic has hookworms
that are resistant to all thedifferent drug classes that are
available on the market.
And so that's where ourinterest in Imodev site sparked,
(05:48):
because people read thatarticle and they would then go
and purchase this product andgive it extra label.
So they were giving the catproduct, which is meant for
topical use orally to dogs, andreally that's what sparked my
interest, because I wasconcerned about safety in all
these different dogs that werebeing treated this way.
Lisa Fortier (06:12):
Yeah, I can see why that would happen.
Stephanie, we heard fromTheresa some probably surprising
findings, I would think basedon Theresa's expression and her
tone like, ooh, the area underthe curve and the PK and all
those things.
But what did you find the mostsurprising thing from this
article?
Theresa Quintana (06:30):
Well, Truly, I expected that we were going to
find overall higherconcentrations when we gave the
topical feline product orally tothe dogs.
Just because it's solubilized,it has accelerants like alcohols
in it, as opposed to the EUformulation which is modified
(06:52):
release and is going to requiredissolution in order for it to
be solubilized and be absorbed.
I just did not know, or I wassurprised.
I guess that it was aboutthreefold higher concentrations
and I think just the magnitudedifference for me was surprising
.
I was simply just not expectingit.
(07:13):
And then, similarly, when wedid give the topical formulation
topically to the dogs, we hadincredibly low concentrations
and I suspected, just because ofthe physiological differences
between skin for cats and dogs,I suspected it was not going to
be as high, but I did not thinkit would be quite as low as we
found.
(07:33):
So I think just the magnitudewas ultimately the between
routes was quite surprising.
Lisa Fortier (07:40):
Yeah, that actually speaks to safety as
well.
Theresa Quintana (07:42):
Right, Like you know, we often think of
safety as avoiding adverseevents, but if the drug isn't
being delivered and doesn't work, that's a safety issue as well,
and I think it's a really greatreminder for our veterinary
community that, just you know,giving the same drug at the same
dose with differentformulations does not guarantee
(08:03):
the same effect, and I thinkthat's just sometimes we forget,
and so it's a really greatreminder.
Yeah, excellent points.
Sarah Wright (08:10):
I come from the zoo world, where things often
are, you know, extra label usetrying to find indications of
certain species, so always goodinformation to keep in mind.
So, Theresa, what are nextsteps for research in this topic
?
Stephanie Martinez (08:22):
Yeah, great question.
So I think if a canineFDA-approved imidapside product
remains unavailable here in theUS and we continue to rely on
this extra label use of thefeline topical formulation as
just kind of this last linetreatment for these
multi-antelmetic drug-resistanthookworms, then the next
critical step would be toinvestigate whether lower doses
(08:45):
of the feline topical productcan achieve bioequivalence to
the EUK9 product, and thenideally we would pair that with
some clinical efficacy studiesagainst multi-antelmetic
drug-resistant hookworms toensure it's both effective and
safe for use in dogs.
Very cool.
Sarah Wright (09:03):
Now this next question deals with AI, which is
definitely a super interestingtopic in veterinary medicine and
for our listeners.
If you haven't already, youshould definitely read our new
AJVR AI Supplemental IssueArtificial Intelligence in
Veterinary Medicine from Barksto Bytes.
So, Jeba, do you see a role forAI in this area of research?
Jeba Jesudoss Chelladurai (09:22):
So in specifically pharmacokinetic
research, in terms of how we didour study, probably not,
although I would cautionveterinarians and because I
teach vet students, I cautionthem all the time about, you
know, ethical use of AI, butalso making sure that AI is
accurate and what it is sayingwhen it comes to diagnosis and
(09:43):
treatment of our patients,because in some models of AI
they're always not the mostaccurate.
So, especially with extra labeldrug use like this, that's
where my only caution is,especially with extra label drug
use like this.
That's where my only caution is.
But in terms of research, Iknow it's coming.
I unfortunately haven't quiteread your AJVR article yet, but
(10:03):
right now, in thepharmacokinetic aspects of the
research, like we did it, Idon't see a role for AI yet.
Lisa Fortier (10:36):
Yeah, in the journals, what we do.
I update our AI policies forlack of a better word quarterly
because, as Sarah said, it's sorapidly evolving it's hard to
keep up.
But right now I rejected amanuscript.
At least 75% of the referenceswere fake, like completely fake,
so you could tell that theseauthors one.
I'm not sure that the wholemanuscript wasn't faked, but we
have programs that our copyeditors run through everything
(10:57):
to know so they can reformat thereferences and they get flagged
like this isn't real.
So I wrote back to the authorsand I was like rejected flat out
and please don't submit to usagain.
Because even if you did use AIand asked it to generate
references, you should, andasked it to generate references,
you should check them right.
(11:19):
So just be you know, again, ithas a great role.
It's really tricky inscientific writing, and don't
forget, too, anybody who doesupload their information to AI.
You don't know where that goes.
So if you put your researcharticle or your data into AI and
ask it to interpret it, you'vejust lost control of it.
Jeba Jesudoss Chelladurai (11:36):
Right .
A long time ago some IT experttold me if the product is free
to you, then you are the product.
I've always taken that to heart.
Lisa Fortier (11:47):
True Copyright's an issue.
Sarah Wright (11:50):
Yep, nothing's truly free.
And for those of you justjoining us, we're discussing how
topical and oral imodepsideformulations for last-line
treatment of multi-anhylmeticdrug-resistant hookworms, when
given orally to dogs, are notbioequivalent with our guests
Theresa Jeba and Stephanie.
So Jeba, how did your trainingor previous work prepare you to
write this article?
Jeba Jesudoss Chelladurai (12:11):
Yeah, so I'm a veterinarian who
trained in India.
I got my advanced training inveterinary parasitology in the
US and for my PhD I worked ontoxic caracanis, the common dog
ground worm.
I worked on MDR-1, which isalso known as PGP, and my
special interest has been indrug-resistant hookworms.
(12:32):
So when the hookworm resistanceissues came around in 2019 and
2020, I was almost immediatelyinterested.
At the same time, I wasstarting as an assistant
professor at Kansas StateUniversity, so I built my
research program aroundresistance, identifying
knowledge gaps that then I couldfill.
So this was a knowledge gapthat I identified almost
immediately because of safetyissues.
(12:53):
Because of safety issues, one,it triggered my PGP bells
because Imodepside is a PGPsubstrate and in dogs that are
mutant for MDR1, it couldpotentially cause neurological
signs and it will causeneurological signs and so this
kind of tied in my interests inpharmacology, zoonotic nematodes
(13:15):
and then definitely the MDR1piece.
Lisa Fortier (13:19):
Yeah, really great .
We like to ask this question ofeverybody, because veterinary
medicine is such a fabulouscareer and you can go in a lot
of different directions.
So, Stephanie, how about you?
How did your training help youwrite this article?
Theresa Quintana (13:31):
So my PhD training focused on
bioanalytical method development, pharmacokinetics and
regulatory science, which is thefoundation of this work.
And then during my postdoc atthe Program for Individualized
Medicine at Washington StateUniversity's vet school, I
gained a lot of hands-onexperience conducting
pharmacokinetic studies inclient-owned dogs, which helped
(13:52):
us with our recruiting at KansasState.
And then really through myentire career, from
undergraduate until even now asan assistant professor at Utah
State University's brand new vetschool, I've been partnering
with veterinarians to reallytackle clinically relevant
pharmacology questions, whichwas really kind of shaped how
(14:13):
I've approached research likethis.
Lisa Fortier (14:16):
Fantastic Theresa.
How about you Bring it home?
How did your training help youwrite this article?
Stephanie Martinez (14:21):
Yeah, so as Dr Jeba's PhD student I'm kind
of like building on her researchwith PGPs and toxic caricanis.
So that kind of helped me, youknow, understand the
pharmacological and molecularmechanisms behind are relevant
to emidexide.
And then I also have abackground in animal health
regulatory affairs.
(14:41):
So that kind of gave me goodinsight into how formulation,
bioequivalence, drug safety, howthat's all evaluated of the FDA
.
I also have my master's inpublic health and I'm certified
in public health.
So, I think that traininghelped me like kind of
critically assess drug use froma population health and safety
perspective and then kind ofhelped frame that like in a
(15:06):
clinical and regulatoryimplications for off-label use
of imidapside in dogs.
Lisa Fortier (15:11):
Fantastic, what great diversity and approach and
opinion within one problem.
That's awesome.
Sarah Wright (15:18):
Now, this next set of questions is going to be
very important for our listeners, and the first one is going to
deal with the veterinarian'sperspective.
So, jeba, what is one piece ofinformation the veterinarian
should know about?
Emodepside in dogs.
Jeba Jesudoss Chelladurai (15:30):
Okay.
So veterinarians managingsuspected multiple antihelminic
drug resistance cases in hookwebs should not directly jump to
using Imodepside as their firstline of treatment.
First they should first focuson establishing that the dog
that they're dealing withactually has resistant hookworms
using properly timed diagnostictests.
Specifically in this case thatwould be a fecal egg count
(15:52):
reduction test that they canperform or get that test done at
any diagnostic lab that theywork with.
After that they should.
After establishing resistance,they can then use a combination
of Drontal Plus, which hasFabantyl Pyrantyl as the two
actives that are going to workagainst the hookworms, and
topical moxidectin, eitherAdvantage Multi or Equivalent
(16:18):
topical moxidectin, eitherAdvantage Multi or Equivalent,
and then, in case of failurewith that treatment, again
assess through an FECRT.
Then they should reach out forthis VLAN formulation of
Imodevcide.
But that should be the lastline of treatment and while they
do, if they do get to that step, they should exercise caution,
making sure that their patientis not MDR1 mutant.
And if they have an MDR1 mutantdog they should seek other
(16:43):
lines of treatment.
So, amorepside should really beused as a last line of
treatment after making sure thatnothing else works.
In addition, they shouldencourage owners to pick up
after their animals so that theyprevent reinfection, which is
very, very important in dealingwith hookworm cases.
Sarah Wright (17:00):
Yeah, I'm always surprised how many like dog
droppings.
I just see like around.
I'm like this is such a publichealth concern, like pick up
after your pets, please.
It's always wild, but thank youfor providing that decision to
me too.
And on the other side of therelationship, what's one thing
that clients should know aboutthis topic?
Jeba Jesudoss Chelladurai (17:21):
So clients should know about this
topic.
So clients should definitely goto their veterinarians yearly,
take their veterinarian's advice, especially as it relates to
deworming schedules, and reallyread through the instructions
that their veterinarian providesthem or gives them orally,
especially as it pertains toproducts.
So there are some products thatare monthly and they should be
given monthly.
There are some products thatdon't cover hookworms, that are
not monthly, and so in that casethey should consult with their
(17:44):
veterinarians to understandwhich product their pet is on
and, again, as a good owner,they should pick up after their
dogs and dispose of the fecesproperly, because, like I just
mentioned, it is a zoonoticparasite, meaning that hookworm
larvae can penetrate human skinand cause what is known as
cutaneous larval migraines inhumans, and so they should be
(18:07):
aware of that.
Theresa Quintana (18:09):
I might also add and just reiterate what Jeb
has said for owners, which isyou must follow your
veterinarian's written and oralinstructions, especially with
emodepside, and probably themost important thing for an
owner to remember is not to feedyour dog overnight.
So, keep your dog fastedovernight and then do not feed
them for at least four hoursafter administration.
(18:31):
So, emodepside's absorption ismarkedly enhanced with food.
Modepside's absorption ismarkedly enhanced with food, and
so giving the feline topicalformulation off-label, knowing
already that we're getting aboutthreefold higher concentrations
, you can imagine giving thatwith food, we would be really
concerned about toxicity.
So, I think again, justfollowing instructions for
(18:55):
owners, that's very important.
Lisa Fortier (18:56):
I think again, just following instructions for
owners.
That's very important.
Great points, Thank you, guys.
This is very interesting.
Stirs up lots of other ideasfor our journal collections and
other things for the One Healthside of our veterinary
profession.
So as we wind down, we'd liketo ask some fun facts.
So, Jeba, we'll start with you.
What is your favorite animalfact?
Jeba Jesudoss Chelladurai (19:16):
Right .
So thank you for that question.
So my favorite animal fact,which I think is really cute, is
sea otters often hold handswhile they sleep.
This behavior is known asrafting, and because they spend
so much of their time in water,they want to prevent, you know,
floating away while they're atsea.
So they often sleep eitherentangling themselves in kelp
(19:36):
forest or by holding hands, andit's a good way to prevent
drifting away from the group.
That's adorable.
It's cute to see as well.
Lisa Fortier (19:45):
Theresa on a different subject.
When you complete a puzzle, doyou do the border exterior
pieces or do you start with acolor or a theme in the inside?
Stephanie Martinez (19:55):
So I do start with the border exterior
and that's because I need like asatisfying sense of progress
right away to keep going tofinish.
Lisa Fortier (20:05):
Yeah, same with me .
I need some structure to get megoing.
Stephanie, on a differentsubject, what was the first
concert you attended?
Theresa Quintana (20:14):
That's a good question.
I have a very eclectic tasteand this is probably going to
age me, but I went to a Weezerconcert, so a rock band from the
90s.
Sarah Wright (20:30):
But yeah, that's awesome, they're actually coming
back to Chicago in September, Ibelieve.
Theresa Quintana (20:32):
So I was actually looking at going yeah,
it's a great show, they're agreat band, so let's get to here
.
Sarah Wright (20:37):
Thank you, and just thank you all again for
being here today, for submittingyour manuscript to AJVR and for
sharing the findings with ourlisteners.
Theresa Quintana (20:44):
Thank you, yeah, thank you again for having
us, yeah.
Sarah Wright (20:48):
And to our listeners.
You can read Theresa Jeba's andStephanie's article on AJVR.
I'm Sarah Wright with LisaFortier.
Be on the lookout for nextweek's episode and don't forget
to leave us a rating and reviewon Apple Podcasts or whatever
platform you listen to.
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