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.
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.
Authors: M Charalambous; S F M Bhatti; L Van Ham; S Platt; N D Jeffery; A Tipold; J Siedenburg; H A Volk; D Hasegawa; A Gallucci; G Gandini; M Musteata; E Ives; A E Vanhaesebrouck Journal: J Vet Intern Med Date: 2017-05-24 Impact factor: 3.333
Authors: Marios Charalambous; Holger A Volk; Andrea Tipold; Johannes Erath; Enrice Huenerfauth; Antonella Gallucci; Gualtiero Gandini; Daisuke Hasegawa; Theresa Pancotto; John H Rossmeisl; Simon Platt; Luisa De Risio; Joan R Coates; Mihai Musteata; Federica Tirrito; Francesca Cozzi; Laura Porcarelli; Daniele Corlazzoli; Rodolfo Cappello; An Vanhaesebrouck; Bart J G Broeckx; Luc Van Ham; Sofie F M Bhatti Journal: J Vet Intern Med Date: 2019-10-03 Impact factor: 3.333