Idiopathic epilepsy (IE) refractory to phenobarbital (PB), potassium bromide (KBr), or a combination of these drugs remains a significant clinical problem in dogs. Pregabalin (PG) is a new antiseizure drug shown to be effective in rodent seizure models and human clinical trials. Considered the "next generation" of gabapentin, PG's pharmacologic effects have been linked to its interaction with the α2δ subunit of neuronal voltage-gated Ca++ channels. By decreasing Ca++ influx, synaptic release of excitatory neurotransmitters (e.g., glutamate) is reduced.
Based on pharmacokinetic data from normal dogs, a PG dose of 2-4 mg/kg q 8 hrs was administered to 6 dogs with suspected IE refractory to PB, KBr, or the combination of these drugs. Dogs starting at the lower end of dosing were increased by 1 mg/kg weekly to a maximum of 4 mg/kg if tolerated. To qualify for study inclusion, dogs had to satisfy the following criteria, in addition to having characteristic clinical features of IE: accurate seizure logs for at least 3 mos prior to the study; a minimum average of 2 seizures/mo; and plasma [PB] and/or [Br] within therapeutic range. Four of the 6 dogs were receiving both PB and KBr, and one dog each was receiving sole PB or KBr therapy. The mean [PB] was 24.9 ug/mL (range, 19.9-29.4 ug/mL) and the mean [Br] was 2.01 mg/mL (range, 0.6-2.81 mg/mL). Five of the 6 dogs exhibited cluster seizures as their typical pattern. Seizure frequency for 3 mos prior to and 3 mos following the addition of PG treatment was compared for each dog.
Five dogs achieved a final dosing level of 4 mg/kg, and one dog achieved 3 mg/kg. One dog left the study at the owner's request at 38 days following a cluster episode and was considered a drug failure. Seizures were reduced in the post-PG period in the remaining 5 dogs, with seizure reduction ranging from 23% to 79% (mean=52%). Four of these 5 dogs were responders (i.e., a minimum of 50% seizure reduction) with a mean seizure reduction of 59.3%. Side effects attributed to PG were reported in 5 dogs, most notably sedation and ataxia. One dog (on PB and KBr) developed severe pancreatitis after garbage ingestion at the end of the study and was euthanized-this was not considered a PG-related side effect. Plasma PG concentrations were measured via HPLC for all dogs at various times during the study (between 30 and 90 days); with the exception of 1 dog (2.6 ug/mL), all dogs had concentrations within the range considered therapeutic for humans (2.8-8.2 ug/mL). Although preliminary, results of this investigation suggest that PG may be an effective add-on therapy for dogs with refractory IE and that side effects are similar to those reported for its predecessor, gabapentin.