Pharmacokinetics of Single‐Dose Rectal Zonisamide Administration in Normal Dogs

Background

Few medications are available for parental administration to animals with seizures. Rectal administration of medications is often used if the animal cannot be administered oral medications.

Hypothesis/Objectives

To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and PO to dogs.

Animals

Eight healthy research dogs.

Methods

Randomized cross‐over design. Zonisamide, 10 mg/kg, was administered rectally in polyethylene glycol (PEG‐R), rectally in water (H₂O‐R), and as an oral capsule. Plasma zonisamide concentrations were measured until 72 hours after administration. Zonisamide was quantitated by HPLC and plasma concentration versus time curve data was analyzed by using noncompartmental modeling.

Results

Mean maximum plasma zonisamide concentrations (μg/mL) were significantly higher after oral administration (11.56 ± 4.04) compared to H₂O‐R (5.00 ± 1.83) (P = .004). Disappearance half‐life (hours) and mean time to maximum concentration (hours) were not significantly different between methods of administration. Mean relative bioavailability of PEG‐R (85 ± 69%) was significantly higher than that of H₂O‐R (53 ± 37%) (P = .039). Dogs tolerated all dosing forms with no evidence of adverse effects.

Conclusions and Clinical Importance

The vehicle in which zonisamide is dissolved influences rectal bioavailability, with PEG preferred to H₂O‐R. Because of the prolonged time to maximum concentration, rectal administration of zonisamide should not be used to treat status epilepticus in dogs. A dose higher than what was used in this study might be necessary, if currently recommended minimum therapeutic concentrations (10 μg/mL) are to be achieved with a single‐dose administration.