Pharmacokinetics and the effect of application site on a novel, long‐acting transdermal fentanyl solution in healthy laboratory Beagles

Abstract

the effect of application site on a novel, long-acting transdermal fentanyl solution in healthy laboratory Beagles. J. vet. Pharmacol. Therap. 35 (Suppl. 2), 27-33. Application of transdermal drugs to different anatomical sites can result in different absorption characteristics. The pharmacokinetics (PKs) and bioequivalence of a single 2.6 mg ⁄ kg (50 lL ⁄ kg) dose of a novel, long-acting transdermal fentanyl solution were determined when applied topically to the ventral abdominal or dorsal interscapular skin of 40 healthy laboratory Beagles. The PKs were differentiated by a more rapid initial absorption of fentanyl from the dorsal application site. Mean plasma fentanyl concentrations remained above 0.6 ng ⁄ mL from 4 to 96 h in the dorsal application group and from 8 to 144 h in the ventral application group. Bioequivalence analysis demonstrated that the sites were not equivalent; the 90% confidence intervals of the ratio of the geometric means for both the maximum concentration (C max ) and the area under the curve (AUC) were not contained within the 80-125% interval. The C max was 2.34 ± 1.29 (mean ± standard deviation) and 2.02 ± 0.84 ng ⁄ mL for the ventral and dorsal application groups, respectively. The terminal elimination half-lives (t 1 ⁄ 2 ) for both groups were similar with values of 137 ± 58.9 and 117 ± 59.6 h for the ventral and dorsal application site groups, respectively. A mean absorption rate of ‡2 lg AE kg ⁄ h was maintained from 2 to 144 h following dorsal application and from 2 to 264 h following ventral application. These results suggest that transdermal fentanyl solution could be applied as a single dose to the dorsal scapular area 2-4 h prior to surgery with analgesia lasting a minimum of 4 days.(Paper

Analgesia in the Perioperative Period

“…9 A single application applied to the interscapular skin of beagles resulted in plasma concentrations consistent with analgesia 4 hours after administration and lasting for 96 hours. 10 When compared with intermittent injection of other opioids (buprenorphine and oxymorphone), this formulation was found to be effective and safe. 11,12 It should also be noted that the opioid antagonist naloxone was able to reverse the effects of overdose when administered at hourly intervals.…”

Population pharmacokinetics of transdermal fentanyl solution following a single dose administered prior to soft tissue and orthopedic surgery in dogs

“…The minimal fluctuations in the pharmacokinetic profile exhibited by TFS have been demonstrated in several laboratory dog studies (Freise et al. , 2012b,c).…”

“…Following dosing, the systemic concentrations of drug remain relatively constant because of a rapid fentanyl deposition into the stratum corneum, from where fentanyl is then steadily delivered into plasma absent of peaks and troughs. These laboratory studies demonstrated that when applied to the dorsal scapular area, mean plasma fentanyl concentrations remained above 0.5 ng/mL through 96 h postdose administration (Freise et al. , 2012b), a concentration that resides in the analgesic range (Kyles et al.…”

The present and future of opioid analgesics in small animal practice

“…An issue of the Journal of Veterinary Pharmacology and Therapeutics was published in June 2012 with studies on the safety, efficacy, and PK‐PD of Recuvyra ® in dogs (Freise et al ., ,b,c,d; KuKanich & Clark, ; Linton et al ., ; Riviere, ; Savides et al ., ). The drug is applied to the skin 2–4 h before surgery and may provide analgesia after single application for up to 4 days postadministration (KuKanich & Clark, ).…”