Pharmacokinetics of fentanyl delivered transdermally in healthy adult horses--variability among horses and its clinical implications.
The safety and pharmacokinetics of fentanyl, delivered transdermally at a dosage of 60-67 microg/kg, were investigated in six healthy adult horses. Three transdermal fentanyl patches (Duragesic), each containing 10 mg of fentanyl citrate, were applied to the mid-dorsal thorax of each horse and left in place for 72 h. Plasma fentanyl concentrations were periodically measured throughout this period and for 12 h after patch removal. After an initial delay of approximately 2 h, the plasma fentanyl concentration rose rapidly in a fairly linear fashion, reaching a peak at around 12 h; thereafter, it gradually declined in a roughly linear manner over the next 72 h. There was much individual variation, however. The initial delay ranged from 0 to 5.1 h (mean, 1.91+/-2.0 h), Tcmax ranged from 8.5 to 14.5 h (mean, 11.4+/-2.7 h) and Cmax ranged from 0.67 to 5.12 ng/mL (mean, 2.77+/-1.92 ng/mL). In two horses, the plasma fentanyl concentration failed to reach even 1 ng/mL, whereas in the other four horses it was >1 ng/mL for at least 40 h and for at least 72 h in two of these horses. No adverse effects attributable to fentanyl were observed in any of the horses, indicating that this dosage is safe in systemically healthy adult horses. However, it failed to achieve plasma fentanyl concentrations generally considered to be analgesic (>or=1 ng/mL) in about one-third of horses.
Orsini
J A
JA
Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA. orsini@vet.upenn.edu
Moate
P J
PJ
Kuersten
K
K
Soma
L R
LR
Boston
R C
RC
D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006736:Horses / Q000378:metabolism*
D000701:Analgesics, Opioid; D005283:Fentanyl