Pharmacokinetic Evaluation of a Novel Transdermal Ketoprofen Formulation in Healthy Dogs

Abstract

Dogs undergo various surgical procedures such as castration, ovariohysterectomy, and other orthopedic procedures, which are known to cause inflammation and pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are very effective analgesics for alleviating postoperative pain in veterinary medicine. Ketoprofen is currently approved in Australia and the United States for treating different painful conditions in dogs. This study evaluated the pharmacokinetic parameters of ketoprofen after intravenous (IV) and transdermal (TD) administration in healthy dogs. A novel transdermal ketoprofen (TDK) formulation containing 20% ketoprofen, dissolved in a combination of 45:45% isopropanol and Transcutol, along with 10% eucalyptus oil, was developed and evaluated for in vitro dermal permeation using Franz diffusion cells. A crossover study was then conducted to determine the pharmacokinetic parameters of the formulation in six dogs following IV ketoprofen (1 mg/kg) and TDK (10 mg/kg) administration. A liquid chromatography–mass spectrometry (LC-M/MS) method was used to measure plasma concentrations of ketoprofen over time, and a non-compartmental analysis determined the pharmacokinetic parameters. The mean terminal elimination half-life (T½ h), AUC0-t (µg·h/mL), and mean residence time (MRT, h) between IV and TDK groups were 4.69 ± 1.33 and 25.77 ± 22.15 h, 15.75 ± 7.72 and 8.13 ± 4.28 µg·h/mL, and 4.86 ± 1.81 and 41.63 ± 32.33 h, respectively. The calculated bioavailability (F%) was ~7%, with a lag time of 30 min to achieve effective plasma concentrations after the application of TDK.

Ketoprofen as an emerging contaminant: occurrence, ecotoxicity and (bio)removal

“…It is also used to relieve mild to moderate pain, such as headaches, dental pain, menstrual cramps, and postoperative pain. In veterinary practice, KTP is used to reduce fever and inflammation in cattle ( De Koster et al, 2022 ), postoperative rehabilitation of dogs ( Monteiro et al, 2019 ; Ravuri et al, 2022 ), and even to treat injured sea turtles ( Harms et al, 2021 ). Research is ongoing to study the efficacy of KTP for treating other animal species, leading to a wider application range of this drug ( Hu et al, 2021 ; Reynolds et al, 2021 ).…”

“…It is also used to relieve mild to moderate pain, such as headaches, dental pain, menstrual cramps, and postoperative pain. In veterinary practice, KTP is used to reduce fever and inflammation in cattle (De Koster et al, 2022), postoperative rehabilitation of dogs (Monteiro et al, 2019;Ravuri et al, 2022), and even to treat injured sea turtles (Harms et al, 2021).…”

Strategies to Improve the Transdermal Delivery of Poorly Water-Soluble Non-Steroidal Anti-Inflammatory Drugs

“…The transdermal permeation of naproxen was significantly enhanced using the terpene eucalyptol [65]. Ketoprofen delivery was enhanced in both cattle [44] and dogs [66]. Additionally, eucalyptus oil has been used in MEG formulations to enhance the transdermal permeation of meloxicam through rat skin [67].…”