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. (2 μg/kg) or t.d. (nominal dose: 2 μg kg hr ). Plasma concentrations were determined using liquid chromatography-mass spectrometry. Heart rate and respiratory rate were assessed. Extrapolated, zero-time plasma fentanyl concentrations were 6.0 ng/ml (1.7-14.6 ng/ml) after i.v. administration, total plasma clearance was 1.10 L hr kg (0.75-1.40 L hr kg ), 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 , V , and V , 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 occurred 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.

Pharmacokinetics of fentanyl citrate and norfentanyl in Holstein calves and effect of analytical performances on fentanyl parameter estimation

“…Other studies have evaluated the pharmacokinetics of intravenously fentanyl in horses (Maxwell et al., ), sheep (Ahern et al., ; Christou, Oliver, Rawlinson, & Walsh, ), goats (Carroll et al., ) and alpacas (Lovasz et al., ). The mean maximum concentration of 1.5 μg/L reported in our study was less than described by earlier reports in other large animal species when normalized with the input dose (Table ).…”

“…The mean maximum concentration of 1.5 μg/L reported in our study was less than described by earlier reports in other large animal species when normalized with the input dose (Table ). The estimated elimination half‐life of fentanyl in calves was apparently longer compared with other large animal species, such as sheep (3.1 hr), goats (1.2 hr) and alpacas (1.2 hr) (Lovasz et al., ). This must be interpreted with caution, however, as these values are compared to mature animals in these previous studies, and drug metabolism can be different between young and older animals of the same species.…”

“…First calculated for each individual calf, and then combined for a mean value. With the calf cardiac output calculated according to Toutain and Bousquet‐Melou () as follows:In a second step and using the same raw source data, an hypothetical analytical LLOQ of 0.05 ng/ml, as reported in the literature in other species (Lovasz et al., ), was applied and the pharmacokinetic analysis for fentanyl only was repeated using the same workflow as described above.…”

“…Among large animal species, the pharmacokinetics (PK) of i.v. fentanyl has been described in sheep (Ahern, Soma, Rudy, Uboh, & Schaer, ), goats (Carroll, Hooper, Boothe, Hartsfield, & Randoll, ), alpacas (Lovasz et al., ) and horses (Maxwell, Thomasy, Slovis, & Kollias‐Baker, ). In small animals, the i.v.…”

Pharmacokinetics and pharmacodynamics of intravenous and transdermal flunixin meglumine in alpacas

“…There are several drugs that can be administered via the transdermal route including fentanyl and more recently flunixin meglumine. A recent study evaluating the pharmacokinetics of transdermal (TD) fentanyl in alpacas found absorption of the drug to be variable (Lovasz et al, ). To date, there have been no studies evaluating flunixin meglumine in alpacas.…”