Evaluation of fentanyl transdermal patches in rabbits: blood concentrations and physiologic response

Abstract

In the study reported here, we sought to evaluate transdermal fentanyl patches for their ability to achieve detectable plasma concentrations with minimal adverse effects in New Zealand White rabbits. Fentanyl patches were applied to the dorsum after removing hair either by clipping or by application of a depilatory agent. Blood samples were collected every 12 h for a total of 96 h (24 h after patch removal) for determination of plasma fentanyl concentration. At those times, rabbits were assessed for changes in body temperature, heart rate, respiratory rate, and body weight. In rabbits with clipped hair, where rapid hair re-growth was not a mitigating factor, mean plasma fentanyl concentration reached a mean (+/- SEM) peak of 1.11 +/- 0.32 ng/ml at 24 h, decreased to 0.77 +/- 0.21 ng/ml at 72 h, and was negligible at 96 h. In rabbits with depilated hair, peak concentration was obtained at 12 h (6.7 +/- 0.57 ng/ml) and decreased gradually to 0.27 +/- 0.06 ng/ml at 72 h. In a second group of fentanyl-treated rabbits in which hair started growing back within 24 h, plasma fentanyl concentration was not detectable. Control and fentanyl-treated rabbits with clipped hair had no effect from the experimental manipulations other than slight loss in body weight. In the depilatory group, two rabbits appeared moderately sedated during the initial 12-h period, and had decreased respiratory rate for 24 h. In conclusion, rabbits tolerate the transdermal fentanyl patch well. Hair regrowth in rabbits may present a complicating factor that impedes dermal absorption of fentanyl. The application of a depilatory agent lead to early and rapid absorption of fentanyl causing undue sedation in some rabbits and lack of sustained plasma concentrations for the desired three-day period.