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Am J Vet Res. 2012 Apr;73(4):539-45. doi: 10.2460/ajvr.73.4.539.

Bioavailability of a novel midazolam gel after intranasal administration in dogs.

Author information

1
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. boiadeiro66@hotmail.com

Abstract

OBJECTIVE:

To compare the pharmacokinetics of a novel bioadhesive gel formulation of midazolam after intranasal (IN) administration with that of midazolam solution after IN, IV, and rectal administration to dogs.

ANIMALS:

10 (5 males and 5 females) healthy adult Beagles.

PROCEDURES:

Dogs were assigned to 4 treatment groups for a crossover study design. Initially, midazolam solution (5 mg/mL) was administered (0.2 mg/kg) IV to group 1, rectally to group 2, and IN to group 3; a 0.4% hydroxypropyl methylcellulose midazolam gel formulation (50 mg/mL) was administered (0.2 mg/kg, IN) to group 4. Each dog received all 4 treatments; there was a 7-day washout period between subsequent treatments. Blood samples were collected before and after midazolam administration. Plasma concentration of midazolam was determined by use of high-performance liquid chromatography.

RESULTS:

The peak plasma concentration after IN administration of the gel formulation was significantly higher than that after IN and rectal administration of the solution. Mean ± SD time to peak concentration was 11.70 ± 2.63 minutes (gel IN), 17.50 ± 2.64 minutes (solution IN), and 39 ± 14.49 minutes (solution rectally). Mean bioavailability of midazolam was 70.4% (gel IN), 52.0% (solution IN), and 49.0% (solution rectally). Bioavailability after IN administration of the gel formulation was significantly higher than that after IN and rectal administration of the solution.

CONCLUSIONS AND CLINICAL RELEVANCE:

IN administration of midazolam gel was superior to both IN and rectal administration of midazolam solution with respect to peak plasma concentration and bioavailability.

PMID:
22452501
DOI:
10.2460/ajvr.73.4.539
[Indexed for MEDLINE]
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