ABSTRACT The objectives of this study were to evaluate ATIP pharmacokinetics (PK) in healthy Beagle dogs after IM and IN dosing (Phase I), and to compare the rate of reversal of IM versus IN routes for xylazine (XYL) sedation (Phase II). This study was comprised of two sequential, randomized, crossover experiments. The initial PK study dosed ATIP by IN and IM routes without XYL sedation. In the second phase, dogs were sedated with XYL prior to ATIP reversal. Their sedation scores were monitored during this period, and blood sampling began 20 min post reversal. ATIP was quantified in plasma using a validated HPLC–MS/MS method. Plasma concentrations of ATIP rapidly increased and declined after both routes, but C max and AUC were higher after IM dosing ( p < 0.001). Relative IN bioavailability was 33%–50% of the IM dose. Xylazine reversal of sedation was more rapid after IM versus IN ATIP ( p < 0.01), but both routes produced complete reversal within 40 min. In conclusion, IN ATIP was slower than IM for reversing XYL sedation but is a viable route if parenteral administration is not an option. Adjusting the labeled IM ATIP dose may be warranted for IN use to account for lower bioavailability.
Cowan et al. (Sat,) studied this question.