title: Pharmacokinetics of single-dose rectal zonisamide administration in normal dogs.
abstract: 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.
  
  
  OBJECTIVE
  To determine the pharmacokinetic differences in zonisamide when administered rectally in either of 2 vehicles and p.o. to dogs.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY.
authors.forename: D M
authors.initials: DM
authors.lastname: Brewer
authors.forename: S
authors.initials: S
authors.lastname: Cerda-Gonzalez
authors.forename: C W
authors.initials: CW
authors.lastname: Dewey
authors.forename: D
authors.initials: D
authors.lastname: Boothe
authors.forename: K
authors.initials: K
authors.lastname: Van Horne
mesh_terms: D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004285:Dogs / Q000097:blood*; D006207:Half-Life; D007555:Isoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013997:Time Factors; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide
keywords: Bioavailability; Epilepsy; Polyethylene glycol; Seizure; Status epilepticus
references.citation: J Small Anim Pract. 2007 Mar;48(3):134-8
references.pmid: 17355603
references.citation: Vet Clin North Am Small Anim Pract. 2006 Sep;36(5):1107-27, vii
references.pmid: 16984829
references.citation: Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40
references.pmid: 17762320
references.citation: Fundam Appl Toxicol. 1988 Aug;11(2):333-42
references.pmid: 3220211
references.citation: Epilepsy Res. 1998 Apr;30(2):153-8
references.pmid: 9600546
references.citation: Biol Pharm Bull. 1997 Aug;20(8):892-6
references.pmid: 9300137
references.citation: J Vet Intern Med. 1993 Sep-Oct;7(5):318-27
references.pmid: 8263851
references.citation: Top Companion Anim Med. 2013 May;28(2):34-41
references.pmid: 24070679
references.citation: J Small Anim Pract. 1998 Jan;39(1):23-9
references.pmid: 9494931
references.citation: Brain Dev. 2008 Oct;30(9):549-55
references.pmid: 18328657