Maximum volume of nasal administration using a mucosal atomization device without aspiration in Japanese White rabbits

Abstract

Recently, a mucosal atomization device (MAD) has been applied in veterinary medicine. In the present study, the maximum volume of nasal atomization without aspiration using MAD was examined in eight healthy female Japanese White (JW) rabbits. Each rabbit had their head and neck examined by computed tomography before and after nasal atomization with four different doses (0.15, 0.3, 0.45, and 0.6 ml per nostril) of diluted contrast medium (1:2 mixture of iohexol and saline). This was done under general anesthesia by an intramuscular administration of alfaxalone 2.5 mg/kg, medetomidine 40 μg/kg, and butorphanol 0.4 mg/kg, with a 7-day washout period between each treatment. The diluted contrast medium was distributed in the nasal cavity, external nares, and/or oral cavity in all rabbits receiving each treatment. The intranasal distribution volumes of the contrast medium were 287 (250-333) mm 3 [median (interquartile range)] for 0.15 ml, 433 (243-555) mm 3 for 0.3 ml, 552 (356-797) mm 3 for 0.45 ml, and 529 (356-722) mm 3 for 0.6 ml of treatment. The intranasal distribution volume for 0.15 ml treatment tended to be lower than that for 0.6 ml treatment (P = 0.083).The contrast medium was deposited in the trachea in one rabbit (12.5%) and four rabbits (50%) receiving treatments of 0.45 and 0.6 ml per nostril, respectively. The maximum volume of nasal atomization without aspiration into the trachea was 0.3 ml per nostril for the JW rabbits.

The sedative effect of intranasal administration of medetomidine using a mucosal atomization device in Japanese White rabbits

“…In JW rabbits, 0.3 mL is the maximum non-aspiration single dose of INA using the MAD [37]; however, the presence or absence of aspiration in multiple 0.3 mL INAs has not been investigated. Although a total of 0.6 mL of 1 mg/mL medetomidine formulation was administered into both nasal cavities by twice atomization in the MED1.2 treatment developing severe hypoxemia, the rabbits successfully recovered from the hypoxemia by oxygen supplementation.…”

“…Hypoxemia is developed by five potential causes such as alveolar hypoventilation, ventilation-perfusion ratio mismatch, diffusion impairment, right-to-left shunt, and low partial pressure of inspired oxygen [ 28 , 32 ]. In JW rabbits, 0.3 mL is the maximum non-aspiration single dose of INA using the MAD [ 37 ]; however, the presence or absence of aspiration in multiple 0.3 mL INAs has not been investigated. Although a total of 0.6 mL of 1 mg/mL medetomidine formulation was administered into both nasal cavities by twice atomization in the MED1.2 treatment developing severe hypoxemia, the rabbits successfully recovered from the hypoxemia by oxygen supplementation.…”

“…However, a large volume of drug solution may cause aspiration because rabbits tolerate only small intranasal doses [ 31 , 39 ]. We examined a maximum single nasal atomizing (INA) dose to prevent aspiration in Japanese White (JW) rabbits and concluded that ≤0.3 mL per nostril should be administered [ 37 ].…”

Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines

“…have reported that 0.3mL was the optimum volume for intranasal delivery of drugs via the MAD without tracheal aspiration in rabbits. However, with a delivery volume of 0.45 or 0.6mL, the MAD was able to deliver particles to the rabbit trachea ( 81 ). Although these findings demonstrate a proof-of-principle that the MAD syringe can potentially deliver drugs/vaccines to the lower respiratory tract, further investigations are required to evaluate the optimal delivery volume of TB vaccines, particularly in humans.…”

Intranasal Atomization of Ketamine, Medetomidine and Butorphanol in Pet Rabbits Using a Mucosal Atomization Device

“…In veterinary medicine, the MAD has been used for the administration of anticonvulsant and sedative drugs in dogs [ 29 , 30 , 31 , 32 , 33 ]. Recent studies report the use of the MAD for the administration of a single sedative or anesthetic drug, such as medetomidine and alfaxalone, and other molecules, in rabbits [ 34 , 35 , 36 , 37 ]; furthermore, the maximum administrable volume using the MAD without aspiration into the trachea was evaluated in Japanese White rabbits [ 38 ].…”