Post by Niels on Aug 13, 2006 17:09:38 GMT -5
A word from our friends the rabbits (re fenbendazole, toxoplasmosis?, and info on
"antiprotozoal drug pyrimethamine (Daraprim),
associated with trimethoprim-sulfa coupled with non-steroidal
antiinflammatory.")
....
www.medirabbit.com/EN/Neurology/cuniculi/pyrimethamine.pdf
pyrimethamine.pdf (application/pdf Object)
The action of benzimidazoles is slow, and depends rather on their presence
in the gastro-intestinal tract and the blood than on the concentration
present. Benzimidazoles will bind to the tubulin of the parasite and block
it . The assemblage of this dimeric tubulin protein form microtubules, that
plays important functional and structural roles in the parasites (transport
of nutritive molecules, cell division). Benzimidazoles will furthermore
block a certain metabolism of parasites, such as the transport and uptake
of glucose, without affecting the host (rabbit, cat, dog). The properties
of the various benzimidazoles used in the treatment of E. cuniculi varies:
* Albendazole is known to be broken down in the liver into more hydrophilic
products, which decreases its capacity to pass though the brain-blood
barrier; the efficacy of the breakdown products against E. cuniculi is ,
however, not known. The use of albendazole, a drug not licensed for use in
rabbits, has led to the acute death of healthy rabbits or the appearance of
bone marrow failure, although this has not been clinically tested. It was
generally f ound that albendazole was less efficacious that oxibendazole
* Oxibendazole is a rather lipophilic molecule that is not degraded in the
body. The advantag es of oxibendazole advantage are its passage through the
blood-brain barrier into the brain or CNS (Central Nervous System), its
lack of teratogen pr perties in ra bits, and its nondegradation in the
liver, prior to passing in the body, unlike albendazole. It is , how ever,
no yet known to what extent oxibendazole is efficacious against
E. cuniculi, and what are the long-term side effects of this compound.
* Fenbendazole was studied for its preventive and curing properties in
rabbits affected by E. cuniculi and the results have been reported in a
scientific journal ( Veterinary Record, 20 01, pp.47 8-480). This was a
major breakthrough, both because there was scientific data to support the
findings and because this was the first treatment that was believed to cure
( rather than simply control) the condition. It was furthermore shown that
fenbendazole alone crosses the blood-brain barrier in mice. In rare cases,
long-term intake of fenbendazole has been associated with the onset of bone
marrow failure, digestive problems and anorexia, though this was not
clinically investigated.
Lab rabbits have shown a high titer one year after being treated with
fenbendazole and remaining clinically asymptomatic during that year. Those
rabbits, that were euthanized a year after the fenbendazole treatment,
still presented the parasite in their brain. They were nevertheless totally
asymptomatic.
!REMARK: Fenbendazole remains currently the drug of choice for the treatment of E. cuniculi.
Lately however, more and more rabbits treated with one or with several
benzimidazoles compounds showed relapse during the treatment period or
after the treatment was stopped. Recently, several caretakers who have been
treating rabbits long-term with oxibendazole have reported that the
treatment gradually stops working, as if the parasite is developing a
resistance to it. Or could two different parasites infect the rabbit, like
E. cuniculi and toxoplasmosis ?
USE OF PYRIMETHAMINE?
Based on scientific literature or a veterinary's experience, some
alternative drugs are tried in "desperate cases", rabbits that faced
euthanasia. The tried compounds include lufenuron, pyrimethamine (used to
treat toxoplasmosis in rabbits ) or ponazuril and have shown more or less
successful.
A treatment protocol for E. cuniculi was developed based on treatment
against Sarcocystis sp. or Toxoplasma spp. in horses and cats,
respectively, using the antiprotozoal drug pyrimethamine (Daraprim),
associated with trimethoprim-sulfa coupled with non-steroidal
antiinflammatory. The treatment is given during one month in horses and two
weeks in cats. Side effects appear to be rare.
"antiprotozoal drug pyrimethamine (Daraprim),
associated with trimethoprim-sulfa coupled with non-steroidal
antiinflammatory.")
....
www.medirabbit.com/EN/Neurology/cuniculi/pyrimethamine.pdf
pyrimethamine.pdf (application/pdf Object)
The action of benzimidazoles is slow, and depends rather on their presence
in the gastro-intestinal tract and the blood than on the concentration
present. Benzimidazoles will bind to the tubulin of the parasite and block
it . The assemblage of this dimeric tubulin protein form microtubules, that
plays important functional and structural roles in the parasites (transport
of nutritive molecules, cell division). Benzimidazoles will furthermore
block a certain metabolism of parasites, such as the transport and uptake
of glucose, without affecting the host (rabbit, cat, dog). The properties
of the various benzimidazoles used in the treatment of E. cuniculi varies:
* Albendazole is known to be broken down in the liver into more hydrophilic
products, which decreases its capacity to pass though the brain-blood
barrier; the efficacy of the breakdown products against E. cuniculi is ,
however, not known. The use of albendazole, a drug not licensed for use in
rabbits, has led to the acute death of healthy rabbits or the appearance of
bone marrow failure, although this has not been clinically tested. It was
generally f ound that albendazole was less efficacious that oxibendazole
* Oxibendazole is a rather lipophilic molecule that is not degraded in the
body. The advantag es of oxibendazole advantage are its passage through the
blood-brain barrier into the brain or CNS (Central Nervous System), its
lack of teratogen pr perties in ra bits, and its nondegradation in the
liver, prior to passing in the body, unlike albendazole. It is , how ever,
no yet known to what extent oxibendazole is efficacious against
E. cuniculi, and what are the long-term side effects of this compound.
* Fenbendazole was studied for its preventive and curing properties in
rabbits affected by E. cuniculi and the results have been reported in a
scientific journal ( Veterinary Record, 20 01, pp.47 8-480). This was a
major breakthrough, both because there was scientific data to support the
findings and because this was the first treatment that was believed to cure
( rather than simply control) the condition. It was furthermore shown that
fenbendazole alone crosses the blood-brain barrier in mice. In rare cases,
long-term intake of fenbendazole has been associated with the onset of bone
marrow failure, digestive problems and anorexia, though this was not
clinically investigated.
Lab rabbits have shown a high titer one year after being treated with
fenbendazole and remaining clinically asymptomatic during that year. Those
rabbits, that were euthanized a year after the fenbendazole treatment,
still presented the parasite in their brain. They were nevertheless totally
asymptomatic.
!REMARK: Fenbendazole remains currently the drug of choice for the treatment of E. cuniculi.
Lately however, more and more rabbits treated with one or with several
benzimidazoles compounds showed relapse during the treatment period or
after the treatment was stopped. Recently, several caretakers who have been
treating rabbits long-term with oxibendazole have reported that the
treatment gradually stops working, as if the parasite is developing a
resistance to it. Or could two different parasites infect the rabbit, like
E. cuniculi and toxoplasmosis ?
USE OF PYRIMETHAMINE?
Based on scientific literature or a veterinary's experience, some
alternative drugs are tried in "desperate cases", rabbits that faced
euthanasia. The tried compounds include lufenuron, pyrimethamine (used to
treat toxoplasmosis in rabbits ) or ponazuril and have shown more or less
successful.
A treatment protocol for E. cuniculi was developed based on treatment
against Sarcocystis sp. or Toxoplasma spp. in horses and cats,
respectively, using the antiprotozoal drug pyrimethamine (Daraprim),
associated with trimethoprim-sulfa coupled with non-steroidal
antiinflammatory. The treatment is given during one month in horses and two
weeks in cats. Side effects appear to be rare.