5 times overdose of moxidectin in 13 day old Arabian foal
This case report describes an approximately 5 times overdose of moxidectin in a 13 day old Arabian/Thoroughbred foal. It presents some information on the use and pharmacokinetics of moxidectin as well as the use of sarmazenil, a benzodiazepine antagonist manufactured in Switzerland.
A 13 day old Arabian/Thoroughbred filly was presented to the University of Zurich with neurological signs after receiving a moxidectin dose of 2 mg/kg BW. On admission, the foal was unconscious and nonresponsive to stimulation. Early treatment included warming techniques, nasogastric tube feeding, IV fluids, IV plasma, Oxygen, ranitidine, and ceftiofur. The foal was stabilized after 15 hours of treatment but remained recumbent and unconscious. Sarmazenil (0.04 mg/kg IV every 2 hours for 5 doses) was added to counteract the neurological effects of moxidectin. After three injections the foal was able to raise its head; after the fifth injection it made attempts to stand. Several hours later it was able to stand and suckle. The nasogastric tube was removed 36 hours after sarmazenil therapy was instituted. Some abnormalities in liver enzymes and white blood cell count occurred, but the foal was discharged clinically normal on day 5. A three month check showed the foal in good health.
Moxidectin has a wide margin of safety in most animals. It may be troublesome in neonates and younger animals with poorly developed brood brain barriers. P-glycoproteins in the blood brain barrier, responsible for maintaining appropriately low concentrations of moxidectin in the central nervous system, may not function as efficiently in neonates.
Moxidectin is a liphophilic, macrocyclic lactone in the milbemycin group. It exerts its effects in nematodes and arthropods by binding to glutamate gated chloride channels. The toxicity of moxidectin, as well as ivermectin/aevermectin, is due to its ability to potentiate GABA (?-aminobutyric acid), an inhibitory neurotransmitter. It stimulates GABA secretion at the synapses and increases GABA binding at postsynaptic receptor sites. The net result is membrane hyperpolarization and opening of the chloride channels.
Sarmazenil was used because it is a competitive antagonist at the benzodiazepine binding site of the GABA receptor in the central nervous system. Based on this mechanism of action, it was hypothesized that sarmazenil might work in a similar manner and “counteract the action of moxidectin at the GABA receptor by down-regulating chloride conductance”. Dose and dosing interval were based on the drug's ability of counteract climazolam, a benzodiazepine drug, in horses. Treatment was continued until response to therapy occurred (i.e. the foal made an attempt to stand on its own).
It is difficult to say if the foal would have improved without the use of sarmazenil. The rapid response in such a young foal certainly makes it an inviting treatment option. At least two other foals have recovered from presumed moxidectin overdoses with only supportive care, although the time frame was much longer. Well planned, scientific studies are needed to determine if sarmazenil is a valid treatment option.
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