The Use of Minipigs for Testing the Local Intranasal Toxicity of Fentanyl

Abstract

The local intranasal toxicity of a nasal formulation of the opioid analgesic fentanyl was investigated in this  study. Minipigs were used as the experimental model. Fentanyl was administered using the formulation and  the device intended for human use. Doses of 400 μg fentanyl were administered 5 times daily to the minipigs  for 4 weeks. In addition, the spreading pattern of the formulation in the minipig nasal cavity was investigated  by applying a formulation containing methylene blue at necropsy. 

Results: The methylene blue spread to the middle parts of the endoturbinates. The No-Observed-Adverse-  Effect-Level (NOAEL) of intranasally administered fentanyl in minipigs was documented to be above 5 x  400 μg/day. After necropsy, no relevant treatment related macroscopic or microscopic findings were  observed, but minimal focal deciliation/degradation of the respiratory epithelium was seen in one animal.  In conclusion, intranasal administration of 400 μg fentanyl 5 times daily for a period of 4 weeks did not  cause any treatment related changes in the nasal cavity of the minipig.