MINIMAL IMPACT OF FOOD, DRINK, OR TEMPERATURE ON THE PHARMACOKINETICS OF A SUBLINGUAL FILM USING AA NOVEL PRODRUG OF EPINEPHRINE (DESF)

Abstract

<h3>Introduction</h3> DESF is a novel alternative dosage form to Epinephrine injection. A pre-clinical study was conducted to test the effect of sublingual temperature (SL) and if exposure of the sublingual mucosa to food or drink prior to administration of DESF has an impact on the PK profile of epinephrine <i>in vivo</i>. <h3>Methods</h3> A total of 18 male Yucatan miniature swine, separated into three groups and dosed with DESF 12 mg, were used for this study. Group 1 did not receive a pre-treatment. Groups 2 and 3 were pretreated with either full-fat whole milk or extra virgin olive oil or with either warm or cool compresses at the dose site. Following dosage, the animals had Pharmacokinetics (PK) blood samples obtained at multiple timepoints, with Oral Mucositis Assessment Scale scores performed at pre-dose, 4-, and 24-hours post-dose. <h3>Results</h3> Similar PK profiles were observed for epinephrine regardless of pretreatment of food and drink. Groups pretreated with milk or oil displayed a mean Cmax and AUC similar to or higher than the control group. Tmax was similar for all treatment groups, between 25 to 30 minutes. As for the impact of temperature, pre-treatment with a warm or cool compress did not result in significantly different SL temperatures. Similar PK profiles were also observed for epinephrine regardless of pre-treatment. Simple linear regression analysis suggests that there was not a strong relationship between SL temperature and Cmax. <h3>Conclusion</h3> These results suggest that food, drink, and temperature each have minimal impact on the PK profiles of DESF.