Pharmacokineticsof tramadol following intranasal administration in dogs undergoing ovariohysterectomy

The intranasal (IN) administration of analgesic drugs represents a non-invasive alternative to oral treatment. It usually ensures a good absorption, avoids the first-pass metabolism and results in a fast onset of action. The aim of this study was to evaluate the pharmacokinetics of IN administration of tramadol in dogs undergoing ovariohysterectomy, compared to its IV administration. Thirteen bitches received the same pre- and intraoperative anaesthetic/analgesic protocol and surgical procedure. At the end of surgery, dogs were randomly assigned to two different groups, and administered with 4 mg kg-1 tramadol IV or IN (six and seven dogs, respectively). At prefixed time-points (before and up to 8 h post treatment) blood samples were taken in order to quantify the concentrations of tramadol and its active metabolite M1 by HPLC-FLU. Following IN administration, tramadol appeared in the systemic circulation 5 min after treatment in six of out of seven dogs; the tramadol maximum plasma concentrations ranged from 74.74 to 198.15 ng mL-1 and were achieved at 0.75 hours post-administration (median value). Following non-compartmental analysis, terminal half-life of elimination was similar to that obtained after IV administration (1.33 vs 1.19 hours respectively); the bioavailability was 9.48%. M1 was detected only in traces (less than 30 ng mL-1) in all subjects treated IV, but only in one treated IN. Further studies are required to establish if, despite the low bioavailability, the IN route could provide analgesic activity due to a direct passage of the drug in the brain via the olfactory and/or trigeminal nerve pathway