Pharmacokinetics of intravenous and transdermal fentanyl in alpacas.

Abstract

The purpose of the study was to determine pharmacokinetics of fentanyl after intravenous (i.v.) and transdermal (t.d.) administration to six adult alpacas. Fentanyl was administered i.v. (2μg/kg) or t.d. (nominal dose: 2μgkg-1 hr-1 ). Plasma concentrations were determined using liquid chromatography-mass spectrometry. Heart rate and respiratory rate were assessed. Extrapolated, zero-time plasma fentanyl concentrations were 6.0ng/ml (1.7-14.6ng/ml) after i.v. administration, total plasma clearance was 1.10Lhr-1 kg-1 (0.75-1.40Lhr-1 kg-1 ), volumes of distribution were 0.30L/kg (0.10-0.99L/kg), 1.10L/kg (0.70-2.96L/kg) and 1.5L/kg (0.8-3.5L/kg) for V1 , V2 , and Vss , respectively. Elimination half-life was 1.2hr (0.5-4.3hr). Mean residence time (range) after i.v. dosing was 1.30hr (0.65-4.00hr). After t.d. fentanyl administration, maximum plasma fentanyl concentration was 1.20ng/ml (0.72-3.00ng/ml), which occurred at 25hr (8-48hr) after patch placement. The area under the plasma fentanyl concentration-vs-time curve (extrapolated to infinity) after t.d. fentanyl was 61ng*hr/ml (49-93ng*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 50μg/hr (29-81μg/hr) between 8 and 72hr after patch placement.