Pharmacotherapeutic group: Nervous system, other antiepileptics
ATC vet code: QN03AX16
5.1 Pharmacodynamic properties
Pregabalin binds to the auxiliary subunit (alpha2-delta protein) of voltage-gated
calcium channels in the central nervous system thereby reducing the release of
various neurotransmitters (glutamate and monoaminergic neurotransmitters) and
producing its anxiolytic effect.
5.2 Pharmacokinetic particulars
Absorption
Pregabalin is rapidly absorbed after oral administration in cats. The Cmax in plasma
was 10.1 μg/ml and occurred at 0.5–1.0 hours after administration of 5 mg/kg
bodyweight into the mouth of cats in fasted state. The area under plasma
concentration-time curve (AUC0-24h) in fasted state was 129 μg*h/ml. The mean
absolute oral bioavailability of pregabalin was 94.3%. After re-dosing of 5 mg/kg at
24 hours, the exposure, in terms of Cmax, AUC0-24h, and t1/2, was comparable with the
exposure following single dosing. No significant differences were noted in overall
absorption, expressed as plasma Cmax and AUC, after administration of pregabalin
into the mouth under different feeding regimes.
Distribution
Pregabalin has a relatively large volume of distribution. After intravenous bolus
administration, the volume of distribution at the steady state (Vss) was 0.4 l/kg.
Pregabalin is not known to bind to plasma proteins in mice, rats, monkeys or humans. This has not been studied in cats.
Metabolism and excretion
Pregabalin is quite slowly eliminated from the body of cats. Total plasma clearance
was 0.03 l/h/kg. The mean half-life of elimination from circulation was 12.3 hours
after intravenous administration of 2.5 mg/kg and 14.7 hours after oral administration
of 5 mg/kg.
Elimination of the parent compound as well as the methylation metabolite from
circulation occurs almost exclusively by renal excretion in rats, monkeys and humans. In dogs, approximately 45% of the pregabalin dose is excreted in urine as
N-methyl metabolite. This has not been studied in cats.