Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 16 ANTICONVULSANT DRUGS
excreted unchanged in the urine. Hepatic metabolism
does occur, resulting in liver enzyme induction and
causing plasma levels of felbamate to decline with longer
duration of drug administration. Peak plasma concentrations
occur 3–5 h after oral dosing, with an elimination
half-life of 5–6 h.
Adverse effects
● The toxicity is low; adverse effects in dogs are not
evident with dosages below 300 mg/kg/d.
● Adverse effects at higher doses in dogs include ataxia,
limb rigidity, tremors, salivation, emesis, reduction
in bodyweight, elevation of ALT, liver disease and
seizures.
● In humans, there is an increased incidence of aplastic
anemia and liver toxicity.
Known drug interactions
None known.
Gabapentin
Clinical applications
In 1994 gabapentin was approved for use as an anticonvulsant
for the control of partial seizures with or
without secondary generalization in humans in the
United States. Gabapentin is an analog of GABA and is
generally used in addition to other anticonvulsant drugs
in humans with intractable epilepsy, including generalized
tonic-clonic and partial seizures. It is well tolerated
in humans and has the advantage of not undergoing
hepatic metabolism.
Although there are anecdotal reports of gabapentin
as an anticonvulsant in dogs, studies of its clinical efficacy
in dogs and cats are lacking.
Mechanism of action
Although the exact mechanism of its anticonvulsant
action is not understood, gabapentin is known to bind
to receptors in the brain and as a result inhibit voltagedependent
sodium currents. It also may enhance the
release of GABA.
Formulations and dose rates
The trade name is Neurontin®.
DOGS
• 25–60 mg/kg PO divided q.6 h or q.8 h
methylgabapentin but it is not known whether this has
anticonvulsant activity. In urine, N-methylgabapentin
accounts for about 32% of a single 50 mg/kg oral
dosage. Elimination is primarily by the kidney. In dogs
the elimination half-life is 3–4 h compared to 5–6 h in
humans.
Adverse effects
● In humans, reported adverse effects include
excessive sedation, gastrointestinal irritation, ataxia
and dizziness.
● In dogs sedation and gastrointestinal irritation are
reported.
● The dosage is reduced in people with impaired
renal function.
Known drug interactions
Pharmacokinetic drug interactions have not been
reported in animals.
Zonisamide
Clinical applications
Zonisamide is a sulfonamide-based anticonvulsant
approved for use in humans but not in animals. It is
used most frequently as an add-on therapy for dogs
already receiving anticonvulsants. Zonisamide should
be used with caution in dogs with renal or hepatic
impairment. There are few reports on the use of
zonisamide in dogs and none in cats. Serum concentrations
of zonisamide may be measured.
Mechanism of action
The mechanism of action is not known. Proposed mechanisms
include: blockage of T-type calcium channels;
alteration of dopaminergic metabolism in the CNS;
scavenging free radical species; enhancement of the
action of GABA in the brain; and inhibition of carbonic
anhydrase activity.
Formulations and dose rates
The trade name is Zonegran®. Zonisamide is available as 25, 50 and
100 mg capsules. Due to its low solubility, a parenteral form has not
been developed.
• DOGS: 10 mg/kg PO q.12 h
• CATS (anecdotal): 5 mg/kg PO q.12
Pharmacokinetics
Gabapentin is well absorbed after oral administration
and is not plasma protein bound. In dogs, unlike
humans, gabapentin is metabolized to N-
Pharmacokinetics
Zonisamide is absorbed rapidly after oral administration.
It has low plasma protein binding. Zonisamide is
mostly excreted unchanged in the urine although about
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