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

Abstract

A novel, long-acting transdermal fentanyl solution (TFS) that delivers sustained plasma fentanyl concentrations following a single application for the control of postoperative pain has recently been approved for use in dogs. The pharmacokinetics (PKs) of this formulation have been evaluated in healthy laboratory dogs, but they have not been reported in a clinical population of dogs for which it is indicated. Plasma fentanyl concentrations were determined from 215 dogs following a single, small-volume ($50 lL ⁄ kg) dose of TFS administered 2-4 h prior to orthopedic or soft tissue surgery. A population PK model was fit, and a 1-compartment open PK model with first-order absorption and an absorption lag-time best described the data. No tested clinical covariates had a significant effect on the PKs. The final model adequately described the population PKs and gave results consistent with laboratory PK studies in healthy dogs. The PKs were primarily characterized by a rapid initial increase in plasma fentanyl concentrations and a long terminal half-life of 74.0 (95% C.I. [54.7-113]) h governed by flip-flop kinetics for the typical subject. The plasma fentanyl concentrations were sustained over days in the range considered to be analgesic for postoperative pain in dogs.

The effectiveness of a long‐acting transdermal fentanyl solution compared to buprenorphine for the control of postoperative pain in dogs in a randomized, multicentered clinical study

“…Rectal temperature differences did not have any apparent clinical significance, and these data support the notion that postoperative hypothermia following TFS is not a primary concern requiring additional case management intervention. In addition, population PK analysis from a randomized clinical trial in dogs treated with TFS prior to orthopedic or soft tissue surgery suggests that fentanyl flux and analgesia are maintained in the presence of decreased body temperature during the postoperative period (Freise et al ., 2012a).…”

Guidelines for Recognition, Assessment and Treatment of Pain

“…A new long‐acting transdermal fentanyl solution has been shown to produce similar postoperative analgesia to buprenorphine in dogs undergoing surgery. Population pharmacokinetics and safety of this compound have been reported in this species . Transdermal patches (fentanyl, lidocaine and buprenorphine) are adhesive patches that are placed on the skin to deliver a specific dose of drug through the skin and into the plasma.…”

The history and pharmacology of fentanyl: relevance to a novel, long‐acting transdermal fentanyl solution newly approved for use in dogs

“… Population plasma fentanyl pharmacokinetics of 215 dogs administered 2.6 mg/kg transdermal fentanyl solution in a randomized field study (Freise et al. , 2012a).…”

“…TFS is not a device like a dermal patch where flux of fentanyl is influenced by outside factors such as external heat. When intra‐operative external heat was applied to approximately 85% of 249 dogs in a randomized clinical trial, postoperative analgesic fentanyl concentrations were maintained without enhanced transdermal flux (Freise et al. , 2012a).…”