Plasma Concentration of Butorphanol in Northern
Royal Albatross Undergoing Fracture Repair
Preet Singh1*, Brett Gartrell1, Craig Johnson1 and Paul Chambers1
1Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Tennant Drive, Palmerston North, New Zealand
Preet Singh, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Tennant Drive, Palmerston North New Zealand. Tel: +6463569099 E-mail:
Received: 28 February, 2018; Accepted: 13 March, 2018; Published: 16 March, 2018
Preet Singh, Gartrell B, Johnson C, Paul C (2018) Plasma Concentration of Butorphanol in Northern Royal Albatross Undergoing Fracture Repair. SOJ Vet Sci 4(2): 1-3. DOI: 10.15226/2381-2907/4/2/00155
Aims: The objective of this study was to determine the plasma
concentration of butorphanol injected intravenously at 4mg/kg
dose in Northern Royal Albatross and compare the pharmacokinetic
parameters with that of broiler chickens.
Methods: The plasma concentration of butorphanol was analysed
by High Performance Liquid Chromatography. The pharmacokinetic
parameters were calculated by non-compartmental approach using
standard equations in spreadsheet.
Results: The half-life, volume of distribution, clearance, mean
residence time were 94.4 minutes, 860.5 ml/kg, 6.31 ml/kg/min, and
146.4 minutes, respectively. The levels remained above the minimum
effective concentration for mammals for about 4 hours.
Conclusion: Though we have data from only one albatross for
butorphanol kinetics, it confirms the chicken data: butorphanol does
not last as long in birds as in mammals. This shows that dose regimes
for mammals are unsuitable for injured wild birds, but we can use
chickens as a model for other wild bird species. The levels remained
above the minimum effective concentration for mammals
Clinical Relevance: Butorphanol can provide good post operative
analgesia in wild birds. The broiler chickens may be used as a model of
drug research for wild birds, but further work is required to establish
Avian veterinarians always face problems while deciding
the dosing regimen of drugs to be used for treatment of various
conditions in birds. Reason being the scarcity of information on
pharmacology of even the most commonly used drugs in birds.
Class Aves, contains 9702 species and such myriad number makes
it impossible to conduct pharmacokinetics in each and every wild
species. There is no established model of drug research for avian
species. This fact also stands true for pharmacology of analgesic
drugs in birds. Butorphanol is the recommended analgesic drug
for birds. Birds have higher number of kappa receptors and
butorphanol being a kappa agonist is the analgesic of choice in
case of birds. Butorphanol improved the welfare and increased
the walking ability of lame turkeys [1,2]. Analgesic efficacy of
butorphanol was also demonstrated by isolfurane sparing effect.
Butorphanol when injected intramuscularly at 1 mg/kg dose
reduced the effective dose for isoflurane in Cockatoos. At this
dose rate, butorphanol also increased the threshold for electrical
stimulus in African grey parrots [3,4]. Sladky et al. 2006, found
that analgesic effects of butorphanol did not last long after
intramuscular injection at 5 mg/kg . They used liposome
encapsulated Butorphanol to increase the duration of analgesia.
The analgesic efficacy of liposome encapsulated butorphanol was
also demonstrated in Conures and Hispaniolan Parrots . Other
methods such as slow release butorphanol formulations and mini
osmotic pumps have been used to increase the duration of action
of butorphanol in birds. Butorphanol is also a safe drug to use for
perioperative analgesia [7,8,9]. Thus, butorphanol is commonly
used for pre and post operative analgesia in birds.
A Northern Royal Albatross, 8 months old, was admitted to
the wild life ward of Massey University Teaching Hospital with
the history of sore left leg. The effected leg was radiographed
under isoflurane anaesthesia. Radiographs showed a long oblique
femur fracture with mild displacement. The fracture was fixed by
placing an intra-medullary pin and external fixator. The surgery
was performed under isoflurane anaesthesia. Butorphanol
injection 10mg/mL (Lloyd Laboratories, New Zealand) was
injected intravenously at 4-mg/kg dose rate. Intravenous fluid
line was set up in the left wing vein for fluids given at 10 mg/kg/
hr. Blood samples were taken at 0, 0.25, 0.5, 1, 1.5, 2 and 4 hours.
The vials were kept chilled immediately after collection and were
centrifuged at 3000 rpm for 10 minutes. Plasma was pipetted
out and kept at -70⁰C until day of analysis. The recovery from the
surgery was smooth. The procedure from start to finish took 1.5
hours. Augmentin 50mg/kg was given intravenously during the
Biochemical analysis of blood was unremarkable with
elevated Creatinine Kinase (CK) which was expected due to
muscle trauma. Rest of the biochemical profile was normal with
no elevation in liver enzymes and normal salts and proteins.
The plasma samples were analysed by high performance
liquid chromatography described elsewhere . Briefly, The
High Performance Liquid Chromatography (HPLC) system
consisted of LC-20AD pumps, SIL-20AC HT auto-injector, Diode
array detector SPD- M20A, CTO-20A column oven, DGU-20A3
Degasser (Shimadzu Japan). The chromatographs were analysed
in LC solutions. The analytical column used was Phenomenex
C18 (2) (150 X 4.6 mm I.d, 5μm particle size). The mobile phase
consisted of 0.1M phosphate buffer pH 4.8: Acetonitrile (80:20)
with flow rate of 1.0 ml/min. The separation was achieved under
isocratic conditions at 30⁰C. The injection volume was 50μl and
the Diode Array Detector (DAD) was set at 202 nm wavelength.
The plasma samples were prepared by the solid phase
extraction procedure using Phenomenex Strata X Reversed Phase
Solid Phase Extraction (SPE) cartridges. The standard solution
used to spike the plasma samples was prepared in the Milli-q
water. 300μL of plasma was spiked with 300μL of the standard
solution and 300μL of concentrated hydrochloric acid was added
and vortex mixed for 1 minute. Then this solution was centrifuged
at 3000 rpm for 10 minutes. The supernatant was separated and
loaded into the SPE cartridge preconditioned with 1 volume of
methanol followed by 1 volume of water. The first wash used 3
ml of water and dried for 2 minutes followed by a second wash
with 2 mL of 40 % methanol and again the cartridge was dried
for 2 minutes. The elution was made with 100% methanol. The
sample was dried under gentle stream of air at 20°C and was
reconstituted with 200μL of mobile phase. The injection volume
was 50μl and each sample was injected three times in the HPLC
All the chromatograms were analysed for peak height, area,
width and the concentration for the unknowns using the software
LC solutions (Shimadzu). The standard calibration curve was also
processed in the same software.
Pharmacokinetic parameters were calculated using standard
equations in a spreadsheet (Excel, Microsoft). These included
half life of the terminal phase (T1/2 ƛz), area under the curve
extrapolated from time zero to infinity (AUC 0-∞), area under
the moment curve extrapolated from time zero to infinity (AUMC
0-∞), volume of distribution (Vd), clearance (Cl) and Mean
Residence Time (MRT).
The semi log plot of concentration time curve for butorphanol
after intravenous administration at 4 mg/kg in albatross is shown
in figure 1. The pharmacokinetic parameters thus calculated
are given in table 1. The terminal half-life (minutes), volume of
distribution (mL/kg) and clearance (mL/min/kg) were 94.4,
860.5 and 6.3, respectively.
Butorphanol is recommended for providing analgesia
in avian species. Despite of that, not much information is
available on its pharmacokinetics in different birds. An injured
Figure 1: Semi-log plot of concentration time curve for Butorphanol after
intravenous administration at 4 mg/kg in Northern Royal Albatross
Table 1: Pharamcokinetic parameters of for butorphanol after
4mg/kg intravenous dose rate in Northern Royal Albatross (n=1).
The pharmacokinetic parameters were calculated using Non-
AUC (0-∞) ng.min/ml
AUMC ( 0-∞ ) ng.min2/ml
T 1/2ƛ min
MRT ƛ min
C (max) ng/ml
AUC ( 0-∞ ) Area under the concentration time curve from time zero to
AUMC ( 0-∞ ) Area under Moment curve from time zero to infinity
Vd Volume of distribution at steady state
T 1/2ƛ min Elimination half life
MRT ƛ min Mean resident time
C (max) ng/ml Maximum concentration (extrapolated)
Albatross was admitted in wild life ward and provided a good
opportunity to analyse the plasma concentration of butorphanol
and to ascertain the time for how long the minimum effective
concentrations in plasma are maintained. The minimum effective
plasma concentration of butorphanol that should be maintained
for analgesia is 50 to 80 ng/mL . In Albatross, after 4 mg/
kg IV. dose rate, the levels of butorphanol were higher than the
minimum effective concentration for 4 hours. No behavioral
analysis were conducted on the albatross, thus these assumptions
about the analgesia were based on the pharmacodynamics study
in chickens. It was assumed that these levels would also provide
good analgesia in albatross. Butorphanol provided analgesia
parrots after 1 and 2 mg/kg intramuscular injection, but it did
not last long [4,5].
Butorphanol was cleared faster in this albatross as compare
to hawks and owls but much slower as compared to chickens
[10,12]. The total body clearance means the amount of drug
cleared per unit time based on the total dose from renal, hepatic
and pulmonary system. As there was no remarkable change in the
kidney and liver function as per the biochemistry profile, there
was no effect on clearane of the drug. Faster clearance in chickens
could be due to smaller body weight and higher metabolic
rate as compared to hawks, owls and albatross. The volume of
distribution was much less in albatross as compared to other
avian species. Volume of distribution describes the distribution
of a drug between its central compartment and rest of the body.
A higher volume of distribution means higher distribution of
drug to various compartments. A lower volume of distribution as
compared to other avian species could be due to the state of the
animal. This albatross was given intravenous fluid therapy and
was in a state of hypovolaemic shock which would decrease the
tissue blood flow and thus reduce the volume of distribution.. In
this study, the number of subjects was only 1 and that too was
an injured albatross, suffering from pain. The distribution and
metabolism of drugs vary with change in physiological state of
This study was not intended to do pharmacokinetics. The
number of subjects in this study was only one, but it presents
valuable information about butorphanol dosing regimens, which
may be used for further used of butorphanol perioperatively in
other injured Albatross or other wild avian species of similar
body weight. Also, there is a need to develop slow release
formulations of butorphanol, which can provide analgesia for a
much longer duration than the standard commercially available
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