J. vet. Pharmacol. Therap.. 2017;1–7. wileyonlinelibrary.com/journal/jvp | 1 © 2017 John Wiley & Sons Ltd Received: 4 April 2016 | Accepted: 14 February 2017 DOI: 10.1111/jvp.12403 ORIGINAL ARTICLE Pharmacokinetics of intravenous and transdermal fentanyl in alpacas M. Lovasz | T. K. Aarnes | J. A. E. Hubbell | R. M. Bednarski | P. Lerche | J. Lakritz Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA Correspondence Turi K. Aarnes, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA. Email: aarnes.1@osu.edu Present address John A. E. Hubbell, Rood and Riddle Equine Hospital, Lexington, KY 40580, USA. Funding information Morris Animal Foundation, Grant/Award Number: Grant Number D15LA-301 The purpose of the study was to determine pharmacokinetics of fentanyl after intrave- nous (i.v.) and transdermal (t.d.) administration to six adult alpacas. Fentanyl was ad- ministered i.v. (2 μg/kg) or t.d. (nominal dose: 2 μg kg −1 hr −1 ). Plasma concentrations were determined using liquid chromatography–mass spectrometry. Heart rate and respiratory rate were assessed. Extrapolated, zero-time plasma fentanyl concentra- tions were 6.0 ng/ml (1.7–14.6 ng/ml) after i.v. administration, total plasma clearance was 1.10 L hr −1 kg −1 (0.75–1.40 L hr −1 kg −1 ), volumes of distribution were 0.30 L/kg (0.10–0.99 L/kg), 1.10 L/kg (0.70–2.96 L/kg) and 1.5 L/kg (0.8–3.5 L/kg) for V 1 , V 2 , and V ss , respectively. Elimination half-life was 1.2 hr (0.5–4.3 hr). Mean residence time (range) after i.v. dosing was 1.30 hr (0.65–4.00 hr). After t.d. fentanyl administration, maximum plasma fentanyl concentration was 1.20 ng/ml (0.72–3.00 ng/ml), which oc- curred at 25 hr (8–48 hr) after patch placement. The area under the plasma fentanyl concentration-vs-time curve (extrapolated to infinity) after t.d. fentanyl was 61 ng*hr/ ml (49–93 ng*hr/ml). The dose-normalized bioavailability of fentanyl from t.d. fentanyl in alpacas was 35.5% (27–64%). Fentanyl absorption from the t.d. fentanyl patch into the central compartment occurred at a rate of approximately 50 μg/hr (29–81 μg/hr) between 8 and 72 hr after patch placement. 1 | INTRODUCTION Fentanyl is a mu receptor opioid agonist commonly used in animals to provide analgesia. The pharmacokinetics of fentanyl have been de- scribed after i.v. administration in dogs (Kukanich & Allen, 2014; Sano et al., 2006), cats (Lee, Papich, & Hardie, 2000; Pypendop, Brosnan, Majewski-Tiedeken, Stanley, & Ilkiw, 2014), horses (Maxwell, Thomasy, Slovis, & Kollias-Baker, 2003; Sanchez, Robertson, Maxwell, Zientek, & Cole, 2007; Thomasy, Mama, Whitley, Steffey, & Stanley, 2007), goats (Carroll, Hooper, Boothe, Hartsfield, & Randoll, 1999), and sheep (Ahern, Soma, Rudy, Uboh, & Schaer, 2010). Plasma concentrations of 0.95 ng/ml of fentanyl are associated with analgesia in dogs (Robinson et al., 1999; Sano et al., 2006). Side effects of fentanyl at relatively high plasma concentrations include respiratory depression in dogs (Arndt, Mikat, & Parasher, 1984) and increased locomotor activity in horses (Kamerling, DeQuick, Weckman, & Tobin, 1985). Documented use of fentanyl in alpacas is limited to a single case report of a 5 μg/kg i.v. bolus given to a neonate to facilitate successful placement of a nasotracheal tube (Tinkler, Mathews, Firshman, & Quandt, 2015). Fentanyl has been formulated as a transdermal (t.d.) patch to fa- cilitate sustained drug delivery. The fentanyl t.d. patch is designed to slowly and consistently release fentanyl (zero-order absorption kinet- ics) to the skin surface where it is absorbed then distributed system- ically via the circulation. Rate of absorption can be affected by body temperature, the amount of body fat present, the location of patch application, and the species in which it is used. Pharmacokinetics of t.d. administration have been evaluated in dogs (Kyles, Papich, & Hardie, 1996; Reed et al., 2011; Schultheiss, Morse, & Baker, 1995), cats (Lee et al., 2000), sheep (Ahern et al., 2010), goats (Carroll et al., 1999), llamas (Grubb et al., 2005), and horses (Eberspächer, Stanley, Rezende, & Steffey, 2008; Maxwell et al., 2003). In llamas, serum fen- tanyl concentrations were first detectable between 12 and 24 hr after