A Critical Review of the Pharmacokinetics and Pharmacodynamics of Opioid Medications Used in Avian Patients
Abstract
:Simple Summary
Abstract
1. Introduction
- (A)
- The lesion or procedure would be painful to other species;
- (B)
- The lesion or procedure is damaging to tissues in other species;
- (C)
- The patient shows any abnormal behaviour [4].
2. Methods
3. Overview of Dosing Regimens of Opioids Used in Avian Species
4. Evaluation of Dosing Regimens in Relation to Efficacy Evidence
4.1. Tramadol
4.2. Hydromorphone
4.3. Buprenorphine
4.4. Butorphanol
4.5. Fentanyl
4.6. Special Formulations of Opioids Impacting Efficacy of Opioids
4.6.1. Buprenorphine
4.6.2. Butorphanol
5. Trends in Efficacy of Selected Opioids
6. Evaluation of Dosing Regimens in Relation to Safety Evidence
7. Pharmacokinetics Variability
7.1. Half-Life
7.1.1. Tramadol
7.1.2. Hydromorphone
7.1.3. Buprenorphine
7.1.4. Butorphanol
7.1.5. Fentanyl
7.2. Bioavailability
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Concept | Keywords |
---|---|
Opioids | Opioid, Opioids, Morphine, Buprenorphine, Butorphanol, Codeine, Hydrocodone, Levorphanol, Meperidine, Tramadol, Methadone, Fentanyl, Hydromorphone, Tapentadol, Oxymorphone, Oxycodone |
Bird | Bird, Birds, Aves, Avian |
Pharmacokinetics and Pharmacodynamics | PK or Pharmacokinetic or Pharmacokinetics or Disposition or Absorption or Absorbed or Bioavailability or Biological Availability or AUC or Area Under the Curve or Area-under-curve or Half life or Half-life or Distribution or Distributed or Volume of distribution or Metabolism or Metabolised or Metabolized or Biotransformation or Metabolic Activation or Metabolic Inactivation or Excretion or Elimination or Clearance or Dosing or Dosage or Dosage Regimen or Dosage Regimens or Therapeutic concentration or Therapeutic concentrations or Therapeutic drug concentration or Therapeutic drug concentrations or PD or Pharmacodynamics or Pharmacodynamic or Analgesia or Analgesic or Analgesics or Analgesic activity or Analgesic activities |
Appendix B
Section and Topic | Item # | Checklist Item | Location Where Item Is Reported |
---|---|---|---|
TITLE | |||
Title | 1 | Identify the report as a systematic review. | NA because it is a critical, not systematic, review |
ABSTRACT | |||
Abstract | 2 | See the PRISMA 2020 for Abstracts checklist. | Abstract Line 21–35 |
INTRODUCTION | |||
Rationale | 3 | Describe the rationale for the review in the context of existing knowledge. | Introduction Line 39–102 |
Objectives | 4 | Provide an explicit statement of the objective(s) or question(s) the review addresses. | Line 106–108 |
METHODS | |||
Eligibility criteria | 5 | Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses. | Method section (line 109–119). Did not include exclusion criteria. |
Information sources | 6 | Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted. | Method section line 110 |
Search strategy | 7 | Present the full search strategies for all databases, registers and websites, including any filters and limits used. | Search term in Appendix A |
Selection process | 8 | Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process. | NA |
Data collection process | 9 | Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. | The first author collected the data |
Data items | 10a | List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g., for all measures, time points, analyses), and if not, the methods used to decide which results to collect. | Method section line 116–119 |
10b | List and define all other variables for which data were sought (e.g., participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information. | NA | |
Study risk of bias assessment | 11 | Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. | NA |
Effect measures | 12 | Specify for each outcome the effect measure(s) (e.g., risk ratio, mean difference) used in the synthesis or presentation of results. | NA |
Synthesis methods | 13a | Describe the processes used to decide which studies were eligible for each synthesis (e.g., tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)). | NA |
13b | Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions. | Conversion of units for some of the data | |
13c | Describe any methods used to tabulate or visually display results of individual studies and syntheses. | NA | |
13d | Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used. | NA | |
13e | Describe any methods used to explore possible causes of heterogeneity among study results (e.g., subgroup analysis, meta-regression). | NA | |
13f | Describe any sensitivity analyses conducted to assess robustness of the synthesized results. | NA | |
Reporting bias assessment | 14 | Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). | NA |
Certainty assessment | 15 | Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. | NA |
RESULTS | |||
Study selection | 16a | Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram. | NA |
16b | Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. | NA | |
Study characteristics | 17 | Cite each included study and present its characteristics. | NA |
Risk of bias in studies | 18 | Present assessments of risk of bias for each included study. | NA |
Results of individual studies | 19 | For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g., confidence/credible interval), ideally using structured tables or plots. | NA |
Results of syntheses | 20a | For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies. | NA |
20b | Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g., confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect. | NA | |
20c | Present results of all investigations of possible causes of heterogeneity among study results. | NA | |
20d | Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results. | NA | |
Reporting biases | 21 | Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed. | NA |
Certainty of evidence | 22 | Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed. | NA |
DISCUSSION | |||
Discussion | 23a | Provide a general interpretation of the results in the context of other evidence. | Section 3, Section 4, Section 5, Section 6 and Section 7 |
23b | Discuss any limitations of the evidence included in the review. | NA | |
23c | Discuss any limitations of the review processes used. | Line 434–436 | |
23d | Discuss implications of the results for practice, policy, and future research. | Section 8 Conclusion | |
OTHER INFORMATION | |||
Registration and protocol | 24a | Provide registration information for the review, including register name and registration number, or state that the review was not registered. | Not registered |
24b | Indicate where the review protocol can be accessed, or state that a protocol was not prepared. | Protocol not prepared | |
24c | Describe and explain any amendments to information provided at registration or in the protocol. | NA | |
Support | 25 | Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review. | Under Funding statement |
Competing interests | 26 | Declare any competing interests of review authors. | Under conflict of interest declaration |
Availability of data, code and other materials | 27 | Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review. | All data presented in the table can be found in the references cited |
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Opioid | Interaction with μ-Opioid Receptor | Interaction with κ-Opioid Receptors |
---|---|---|
Tramadol [19] | Weak agonist | - |
Hydromorphone [20] | Agonist | - |
Buprenorphine [21] | Partial agonist-antagonist | - |
Butorphanol [22] | Mixed agonist/antagonist | Partial agonist |
Fentanyl [23] | Agonist | - |
Drug | Species (English Name) | Species (Scientific Name) | Route of Administration | Age (Years) | Duration of Treatment | Dosing Regimen Studied | Dosing Regimen Found in Exotic Animal Formulary 5th Edition (Yes/No) | Reference |
---|---|---|---|---|---|---|---|---|
Tramadol | Bald Eagle | Haliaeetus leucocephalus | Oral | - | Single dose | 11 mg/kg 1 | Yes | [24,25] |
Intravenous | - | Single dose | 4 mg/kg 2 | |||||
American Kestrel | Falco sparverius | Oral | 3 | Single dose | 5 mg/kg 15 mg/kg 30 mg/kg | Yes | [26] | |
Red-tailed Hawk | Buteo jamaicensis | Oral | - | Single dose | 11 mg/kg 3 | Yes 4 | [25,27] | |
Jackass Penguin | Spheniscus demersus | Oral | 1.5–20 | Single dose | 10 mg/kg | Yes | [28] | |
Hispaniolan Parrot | Amazona ventralis | Oral | - | Repeated dose (BD) for 5 days | 30 mg/kg | Yes | [29,30,31,32] | |
Intravenous | - | Single dose | 5 mg/kg | No | ||||
Indian Peafowl | Pavo cristatus | Oral | - | Single dose | 7.5 mg/kg | No | [33] | |
Muscovy Duck | Cairina moschata | Oral | - | Single dose | 30 mg/kg | No | [7,34] | |
Hydromorphone | American Kestrel | Falco sparverius | Intramuscular | 2 | Single dose | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Yes | [35,36] |
Cockatiel | Nymphicus hollandicus | Intramuscular | 2–6 | Single dose | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Yes | [37] | |
Orange-winged Parrot | Amazona amazonica | Intramuscular | 4–17 and 28–45 | Single dose | 0.1 mg/kg 1 mg/kg 2 mg/kg | No 5 | [38,39] | |
Intravenous | 28–45 | Single dose | 1 mg/kg | No | ||||
Buprenorphine | Grey Parrot | Psittacus erithacus | Intramuscular | - | Single dose | 0.1 mg/kg | Yes 6 | [40,41] |
Intravenous | - | Single dose | 0.1 mg/kg | No | ||||
American Kestrel | Falco sparverius | Intramuscular | 3 | Single dose | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Yes | [42,43] | |
Intravenous | 3 | Single dose | 0.6 mg/kg | No | ||||
Subcutenous (sustained-release) | 3–5 | Single dose | 1.8 mg/kg | Yes | [44,45] | |||
Intramuscular (sustained-release) | 3–5 | Single dose | 1.8 mg/kg | Yes | ||||
Red-tailed Hawk | Buteo jamaicensis | Intramuscular | - | Twice daily | 0.25 mg/kg | Yes | [46] | |
Subcutaneous (concentrated) | - | Single dose | 0.3 mg/kg 1.8 mg/kg | Yes | [47] | |||
Rock Dove | Columba livia | Intramuscular | - | - | Unable to find evidence | Yes | [10] | |
Cockatiel | Nymphicus hollandicus | Intramuscular | 2–6 | Single dose | 0.6 mg/kg 1.2 mg/kg 1.8 mg/kg | No 7 | [48] | |
Butorphanol | Hispaniolan Parrot | Amazona ventralis | Oral | 8 | Single dose | 5 mg/kg | No | [49] |
Intravenous | 8 | Single dose | 5 mg/kg | Yes | ||||
Intramuscular | 8 | Single dose | 2 mg/kg 8 5 mg/kg | Yes | [49,50] | |||
Subcutaneous (long-acting) | - | Single dose | 12 mg/kg | No | [51] | |||
Subcutaneous (liposome-encapsulated) | 11–27 | Single dose | 10 mg/kg 15 mg/kg | No | [50,52] | |||
Grey Parrot and Timneh Parrot | Psittacus erithacus and Psittacus timneh | Intramuscular | - | Single dose | 1 mg/kg | Yes | [41] | |
Red-tailed Hawk | Buteo jamaicensis | Intravenous | - | Single dose | 0.5 mg/kg | Yes | [53] | |
Intramuscular | - | Single dose | 0.5 mg/kg | Yes | ||||
Great Horned Owl | Bubo virginianus | Intravenous | - | Single dose | 0.5 mg/kg | Yes | [53] | |
Intramuscular | - | Single dose | 0.5 mg/kg | Yes | ||||
American Kestrel | Falco sparverius | Intramuscular | 2–3 | Single dose | 1 mg/kg 3 mg/kg 6 mg/kg | Yes | [54] | |
Sulphur-crested Cockatoo and Yellow-crested Cockatoo | Cacatua galerita, Cacatua sulphurea citrinocristata and Cacatua sulphurea sulphurea | Intramuscular | - | Single dose | 1 mg/kg | Yes | [16] | |
Psittacine | - | Constant-Rate Infusion | - | - | Unable to find evidence | Yes 9 | [10] | |
Ratite | - | Intravenous | - | - | Unable to find evidence | Yes 10 | [10] | |
Broiler Chicken | - | Intravenous | - | Single dose | 2 mg/kg | No | [55] | |
Indian Peafowl | Pavo cristatus | Osmotic pump | - | 7 continuous days | 120 μg/kg/hr with rate 48.1 mg/mL 11 | No | [56] | |
Fentanyl | African and New World Parrots | Cacatua alba | Intramuscular | - | Single dose | 0.01 mg/kg 0.02 mg/kg | Yes | [57] |
Subcutaneous | - | Single dose | 0.2 mg/kg | Yes 12 | ||||
Red-tailed Hawk | Buteo jamaicensis | Constant-Rate Infusion | - | - | Unable to find evidence 13 | Yes | [10] | |
Hispaniolan Parrot | Amazona ventralis | Constant-Rate Infusion | - | - | Unable to find evidence 14 | Yes | [10] | |
Helmeted Guineafowl | Numida meleagris | Transdermal | - | Single dose | 5 mg/kg | No | [58] | |
Chickens (Brahma, Delaware, Redstar and Wyandotte) | - | Transdermal | 3 | Single dose | 25 μg/h for 72 h | No | [59] |
Species Name | Dosing Regimen | PD Study | Plasma Concentration | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
English | Scientific | Dose | Administration | Type | Result | Duration | Target (Parent/Metabolite) | Source | Duration ≥ Target Concentration | Reference | ||
Opioid | Metabolite | |||||||||||
TRAMADOL | ||||||||||||
Bald Eagle | Haliaeetus leucocephalus | 11 mg/kg | Oral | - | - | - | 298–590 ng/mL/39.6–84 ng/mL | Human | 10 h; 5/6 birds | 2 eagles; 1 timepoint each | [24,25] | |
4 mg/kg | Intravenous | - | - | - | 298–590 ng/mL/39.6–84 ng/mL | Human | 5 h; 5/6 birds | - | ||||
American Kestrel | Falco sparverius | 5 mg/kg 15 mg/kg 30 mg/kg | Oral | Thermal stimulus | Significant increase in thermal withdrawal threshold. | 9 h for 5 mg/kg; 3 h for 15 mg/kg and 30 mg/kg. | - | - | - | - | [26] | |
Red-tailed Hawk | Buteo jamaicensis | 11 mg/kg | Oral | - | - | - | 298–590 ng/mL/39.6–84 ng/mL | Human | 4 h after dosing | - | [25,27] | |
Jackass Penguin | Spheniscus Demersus | 10 mg/kg | Oral | - | - | - | 298–590 ng/mL/39.6–84 ng/mL | Human | 12 h in 9/15 of birds and 24 h in 1/15 of birds | 36 h in 14/15 of birds | [28] | |
Hispaniolan Parrot | Amazona ventralis | 30 mg/kg | Oral | Thermal stimulus | Significant increase in thermal withdrawal threshold | - | 298–590 ng/mL/39.6–84 ng/mL | Human | 6 h | - | [29,30,31,32] | |
5 mg/kg | Intravenous | Thermal stimulus | Increase in thermal withdrawal threshold | - | - | - | - | [29,30,31,32] | ||||
Indian Peafowl | Pavo Cristatus | 7.5 mg/kg | Oral | - | - | - | 298–590 ng/mL/39.6–84 ng/mL | Human | Up to 2 h in 2 birds | 12 h in 5/6 birds | [33] | |
Muscovy Duck | Carina moschata | 30 mg/kg | Oral | Difference in maximum force between arthritis-induced and non-arthritis induced legs | Significant difference between both tramadol and meloxicam vs. control | Up to 4 h | 298–590 ng/mL/39.6–84 ng/mL | Human | At least 12 h | At least 6 h | [7,34] | |
HYDROMORPHONE | ||||||||||||
American Kestrel | Falco sparverius | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Intramuscular | Thermal stimulus | 0.6 mg/kg—Significant increase in thermal foot withdrawal threshold | 3 h | >1 ng/mL | American kestrel | 0.6 mg/kg —3–6 h | - | [35,36] | |
Cockatiel | Nymphicus hollandicus | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Intramuscular | Thermal stimulus | Did not increase thermal foot withdrawal threshold | - | >1 ng/mL | American kestrel | 0.6 mg/kg—3–6 h | - | [50] | |
Orange-winged Parrot | Amazona amazonica | 0.1 mg/kg 1 mg/kg 2 mg/kg | Intramuscular | Thermal stimulus | Significant increase in thermal foot withdrawal threshold | When administered 1 mg/kg and 2 mg/kg—3 h and 6 h respectively | >1 ng/mL | American kestrel | 1 mg/kg—6 h in 8/8 birds | - | [38,39] | |
1 mg/kg | Intravenous | -1 | - | - | >1 ng/mL | American kestrel | 6 h; 6/7 birds | - | ||||
BUPRENORPHINE | ||||||||||||
Grey Parrot | Psittacus erithacus | 0.1 mg/kg | Intramuscular | Electric stimulus | No significant change in electrical withdrawal threshold | - | >1 ng/mL | Human | 2 h | - | [40,41] | |
0.1 mg/kg | Intravenous | - | - | - | >1 ng/mL | Human | 2 h | - | [40,41] | |||
American Kestrel | Falco sparverius | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Intramuscular | Thermal stimulus | Significant increase in thermal foot withdrawal threshold | All doses tested—6 h | >1 ng/mL | Human | 0.6 mg/kg–9 h 2 | - | [42,43] | |
1.8 mg/kg | Subcutaneous (sustained-release) | - | - | - | > 1 ng/mL | Human | 48 h | - | [44] | |||
1.8 mg/kg | Intramuscular (sustained-release) | Thermal stimulus | Significant increase in thermal foot withdrawal threshold | Up to 24 h | >1 ng/mL | Humans | 48 h | - | [44,45] | |||
0.6 mg/kg | Intravenous | - | - | - | >1 ng/mL | Human | 9 h | - | [43] | |||
Red-tailed Hawk | Buteo jamaicensis | 0.25 mg/kg | Intramuscular | -3 | - | - | - | - | - | - | [46] | |
0.3 mg/kg 1.8 mg/kg | Subcutaneous (concentrated) | - | - | - | >1 ng/mL | Human | 0.3 mg/kg—24 h; 1.8 mg/kg—48 h | - | [47] | |||
Cockatiel | Nymphicus hollandicus | 0.6 mg/kg 1.2 mg/kg 1.8 mg/kg | Intramuscular | Thermal stimulus | No significant increase in thermal withdrawal threshold | - | > 1 ng/mL | Human | 9 h; 4/4 birds | - | [48] | |
BUTORPHANOL | ||||||||||||
Hispaniolan Parrot | Amazona ventralis | 5 mg/kg | Oral | - | - | - | 100 ng/mL | Hispaniolan amazon parrots | - | - | [49] | |
2 mg/kg 4 5 mg/kg | Intramuscular | - | - | - | 100 ng/mL | Hispaniolan amazon parrots | - | - | [49,50] | |||
5 mg/kg | Intravenous | - | - | - | 100 ng/mL | Hispaniolan amazon parrots | - | - | [49] | |||
10 mg/kg 15 mg/kg | Subcutaneous (Liposome-Encapsulated) | Electrical and thermal stimuli | Significant increased in electrical and thermal withdrawal threshold | Up to 5 days | -5 | - | - | - | [50,52] | |||
12 mg/kg | Subcutaneous (Long-Acting) | - | - | - | 100 ng/mL | Hispaniolan amazon parrots | >3 h (all birds) or >4 h (5/8 birds) but < 8 h (all birds) | - | [51] | |||
Grey Parrot and Timneh Parrot | Psittacus erithacus and Psittacus timneh | 1 mg/kg | Intramuscular | Electric stimulus- | Significant increase in electrical withdrawal threshold | - | - | - | - | - | [41] | |
Sulphur-crested Cockatoo and Yellow-crested Cockatoo | Cacatua galerita, Cacatua sulphurea cintrinocristata and Cacatua sulphurea sulphurea | 1 mg/kg | Intramuscular | - | - | - | - | - | - | - | [16] | |
Red-tailed Hawk | Buteo jamaicensis | 0.5 mg/kg | Intravenous | - | - | - | 9–30 ng/mL | Dogs, horses & llamas 6 | 2–4 h | - | [53] | |
0.5 mg/kg | Intramuscular | - | - | - | 9–30 ng/mL | Dogs, horses & llamas 7 | 2–4 h | - | [53] | |||
Great Horned Owl | Bubo virginianus | 0.5 mg/kg | Intravenous | - | - | - | 9–30 ng/mL | Dogs, horses & llamas 8 | 2–4 h | - | [53] | |
0.5 mg/kg | Intramuscular | - | - | - | 9–30 ng/mL | Dogs, horses & llamas 9 | 2–4 h | - | [53] | |||
American Kestrel | Falco sparverius | 1 mg/kg 3 mg/kg 6 mg/kg | Intramuscular | Thermal stimulus | Significantly increased in female compared with baseline but not significant compared with control | - | 100 ng/mL | Humans | 2 h | - | [54] | |
Broiler Chicken | - | 2 mg/kg | Intravenous | - | - | - | 55–70 ng/mL | Unknown | 2 h | - | [55] | |
Indian Peafowl | Pavo cristatus | 120 μg/kg/hr with rate 48.1 mg/mL 10 | Osmotic pump | - | - | - | 60 μg/mL | Hispaniolan amazon parrots | 85.6 h (mean) | - | [56] | |
FENTANYL | ||||||||||||
Chickens (Brahma, Delaware, Redstar and Wyandotte) | - | 25 μg/h for 30 s | Transdermal | - | - | - | 0.2–1.2 ng/mL | Human | 72 h | - | [59] | |
Helmeted Guineafowl | Numida meleagris | 5 mg/kg | Transdermal | - | - | - | 8.51–29.25 ng/mL | Dogs | At least 7 days | - | [58] | |
White Cockatoo | Cacatua alba | 0.01 mg/kg 0.02 mg/kg | Intramuscular | Thermal and electrical stimuli | No increase in electrical and thermal withdrawal thresholds | - | 0.2 ng/mL | Human | 0.02 mg/kg—300 min | - | [57] | |
0.1 mg/kg | Subcutaneous | Thermal and electrical stimuli | Significant increase in thermal and electrical withdrawal thresholds | - | 0.2 ng/mL | Human | - | - | [57] |
Species Name | Dosing Regimen | Adverse Effect | Reference | ||
---|---|---|---|---|---|
English | Scientific | Dose | Administration | ||
TRAMADOL | |||||
Bald Eagle | Haliaeetus leucocephalus | 11 mg/kg | Oral | None observed | [24,25] |
4 mg/kg | Intravenous | Mild transient bradycardia observed immediately after administration until 10 min after IV administration in 3 birds. Bradycardia is deemed clinically insignificant. | |||
American Kestrel | Falco sparverius | 5 mg/kg 15 mg/kg 30 mg/kg | Oral | GI adverse effect observed at higher doses (15 mg/kg and 30 mg/kg). Vomiting observed in 1 kestrel within 30 min after administration of tramadol 30 mg/kg. Polyuria observed for 6 birds—1 control; 2 treated with 15 mg/kg tramadol; 3 treated with 30 mg/kg | [26] |
Red-tailed Hawk | Buteo jamaicensis | 11 mg/kg | Oral | None observed | [25,27] |
Jackass Penguin | Spheniscus Demersus | 10 mg/kg | Oral | Penguins were subjectively quieter 1–1.5 h post administration & considered back to normal after 6 h of administration. This could be due to frequent handling. Monitor for signs of sedation. | [28] |
Hispaniolan Parrot | Amazona ventralis | 30 mg/kg | Oral | No sedation or changes in behavior were detected. Birds had ruffled feathers and were quiet after handling but did not have other signs of stress. | [29,30,31,32] |
5 mg/kg | Intravenous | [29,30,31,32] | |||
Indian Peafowl | Pavo Cristatus | 7.5 mg/kg | Oral | No adverse effects or changes in behavior noted | [33] |
Muscovy Duck | Carina moschata | 30 mg/kg | Oral | No adverse effects noted | [7,34] |
HYDROMORPHONE | |||||
American Kestrel | Falco sparverius | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Intramuscular | Appreciable sedation detected in 4 birds after administration of 6 mg/kg hydromorphone | [35,36] |
Cockatiel | Nymphicus hollandicus | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Intramuscular | Sedation after administration of 0.3 mg/kg and 0.6 mg/kg hydromorphone | [50] |
Orange-winged Parrot | Amazona amazonica | 0.1 mg/kg 1 mg/kg 2 mg/kg | Intramuscular | Treatment was significantly (p < 0.001) associated with nausea-like behavior. Other adverse effect includes ataxia and miosis. | [38,39] |
1 mg/kg | Intravenous | Not reported | |||
BUPRENORPHINE | |||||
Grey Parrot | Psittacus erithacus | 0.1 mg/kg | Intramuscular | Not reported | [40,41] |
0.1 mg/kg | Intravenous | ||||
American Kestrel | Falco sparverius | 0.1 mg/kg 0.3 mg/kg 0.6 mg/kg | Intramuscular | Mild to moderate sedation was recorded within 15 to 30 min after both IM and IV administration of 0.6 mg of buprenorphine/kg, although the birds remained reactive to physical handling at all time points. | [42,43] |
0.6 mg/kg | Intravenous | [43] | |||
1.8 mg/kg | Subcutaneous (sustained-release) | There was no subjectively appreciable sedation after either IM or SC administration.- | [44] | ||
1.8 mg/kg | Intramuscular (sustained-release) | [44,45] | |||
Red-tailed Hawk | Buteo jamaicensis | 0.25 mg/kg | Intramuscular | -1 | [46] |
0.3 mg/kg 1.8 mg/kg | Subcutaneous (concentrated) | Mean agitation-sedation scores were higher (indicating some degree of sedation) than the baseline values for 24 h at both doses. No clinically important adverse effects were observed. | [47] | ||
Cockatiel | Nymphicus hollandicus | 0.6 mg/kg 1.2 mg/kg 1.8 mg/kg | Intramuscular | Did not significantly cause sedative or agitative effects | [48] |
BUTORPHANOL | |||||
Hispaniolan Parrot | Amazona ventralis | 5 mg/kg | Oral | Significant adverse effects were not observed | [49] |
2 mg/kg 2 5 mg/kg | Intramuscular | Significant adverse effects were not observed | [49,50] | ||
5 mg/kg | Intravenous | Significant adverse effects were not observed but 1 parrot developed apnea for a short period. | [49] | ||
10 mg/kg 15 mg/kg | Subcutaneous (Liposome-Encapsulated) | No observable adverse effect although there were mild-moderate sedation between 1–2 h after administration. | [50,52] | ||
12 mg/kg | Subcutaneous (Long-Acting) | All birds were subjectively quieter after administration of butorphanol. Furthermore, 2 birds receiving 16.6 mg/kg SC vomited around 1.31 h post administration. | [51] | ||
Grey Parrot and Timneh Parrot | Psittacus erithacus and Psittacus timneh | 1 mg/kg | Intramuscular | Not reported | [41] |
Sulphur-crested Cockatoo and Yellow-crested Cockatoo | Cacatua galerita, Cacatua sulphurea cintrinocristata and Cacatua sulphurea sulphurea | 1 mg/kg | Intramuscular | Not reported | [16] |
Red-tailed Hawk | Buteo jamaicensis | 0.5 mg/kg | Intravenous | Mild sedation but no significant change in heart and respiratory rates | [53] |
0.5 mg/kg | Intramuscular | [53] | |||
Great Horned Owl | Bubo virginianus | 0.5 mg/kg | Intravenous | Mild sedation but no significant change in heart and respiratory rates | [53] |
0.5 mg/kg | Intramuscular | [53] | |||
American Kestrel | Falco sparverius | 1 mg/kg 3 mg/kg 6 mg/kg | Intramuscular | No sedative effect observed but male kestrels appeared agitated at 1.5 h. | [54] |
Broiler Chicken | - | 2 mg/kg | Intravenous | Not reported | [55] |
Indian Peafowl | Pavo cristatus | 120 μg/kg/h with rate 48.1 mg/mL 3 | Osmotic pump | No evidence of sedation or other adverse effect | [56] |
FENTANYL | |||||
Chickens (Brahma, Delaware, Redstar and Wyandotte) | - | 25 μg/h for 30 s | Transdermal | No adverse effects noted | [59] |
Helmeted Guineafowl | Numida meleagris | 5 mg/kg | Transdermal | No adverse effects noted | [58] |
White Cockatoo | Cacatua alba | 0.01 mg/kg 0.02 mg/kg | Intramuscular | None observed | [57] |
0.1 mg/kg | Subcutaneous | 2/7 birds sedate at 20 min, 6 birds hyperactive between 20 and 60 min | [57] |
Species | Weight | Dosage Studied | Route of Administration | Fed or Fasted | Formulation | Cmax (ng/mL) | Bioavailability (%) | Half-Life (hr) | Reference | ||
---|---|---|---|---|---|---|---|---|---|---|---|
English | Scientific | Parent Drug | Metabolite | ||||||||
TRAMADOL | |||||||||||
Bald Eagle | Haliaeetus leucocephalus | 2.95–5.91 kg | 11 mg/kg | Oral | Fasted 12 h before dosing | Suspension | 2156.7 ± 681.4 | 97.9 | 3.14 ± 0.94 | 6.28 ± 1.72 | [24,25] |
2.95–5.91 kg | 4 mg/kg | Intravenous | - | - | - | 2.46 ± 0.65 | - | ||||
Red-tailed Hawk | Buteo jamaicensis | Not reported | 11 mg/kg | Oral | Fasted 12 h before dosing | Suspension | 1412.3 ± 79.6 | - | 1.3 ± 0.6 | 1.9 ± 0.2 | [25,27] |
Jackass Penguin | Spheniscus Demersus | ≥2.7 kg | 10 mg/kg | Oral | Tramadol given with a fish. No additional fish offered untl 4 h later. | Capsules | - | - | 7.3 ± 1.5 | 13.58 ± 4.38 | [28] |
Hispaniolan Parrot | Amazona ventralis | 319 ± 30 g | 30 mg/kg | Oral | Food withheld 2 h after administration | Suspension | 1.67 ± 1.17 | 23.48 ± 6.96 | 4.85 ± 0.33 | 2.7 ± 0.38 | [29,30,31,32] |
321 ± 28 g | 30 mg/kg | Oral (BD, 5 days) | Food was not withheld | Suspension | 409 ± 132 | - | 2.92 ± 0.78 | 2.14 ± 2.10 | |||
319 ± 30 g | 5 mg/kg | Intravenous | Food withheld 2 h after administration | - | - | 1.54 ± 0.51 | 2.55 ± 0.85 | ||||
Indian Peafowl | Pavo Cristatus | 4.1 ± 0.4 kg | 7.5 mg/kg | Oral | Not fasted. Free access to food. | Suspension | 116.0 ± 79.14 | - | 1.68 ± 0.41 | 5.10 ± 2.29 | [33] |
Muscovy Duck | Carina moschata | 2.6 ± 0.7 kg | 30 mg/kg | Oral | Food withheld 2 h before procedure | Suspension | 780 ± 300 | - | 3.95 ± 0.60 | 1.51 ± 1.21 | [7,34] |
HYDROMORPHONE | |||||||||||
Orange-winged Parrot | Amazona amazonica | 402.6 ± 42 g | 1 mg/kg | IM | Ad libitum access to water and pelleted diet | - | 179.1 ± 28.4 | 97.6 ± 61.1 | 1.74 ± 0.351 | - | [38,39,87] |
402.6 ± 42 g | 1 mg/kg | Intravenous | - | - | - | 1.45 ± 0.270 | - | ||||
American Kestrel | Falco sparverius | 115 ± 6.2 g | 0.6 mg/kg | IM | No access to food or water throughout blood sample collection | - | 112.10 | 75 | 1.25 | - | [35,36] |
115 ± 6.2 g | 0.6 mg/kg | Intravenous | - | - | - | 1.26 | - | ||||
Cockatiel | Nymphicus hollandicus | 78.5–130.8 g | 0.6 mg/kg | IM | Ad libitum access to water and pelleted diet | - | 135.8 | - | 0.99 | - | [37] |
BUPRENORPHINE | |||||||||||
Grey Parrot | Psittacus erithacus | 300–500 g | 0.1 mg/kg | IM | - | - | 68.7 | - | 1.04 ± 0.14 | - | [40,41] |
300–500 g | 0.1 mg/kg | Intravenous | - | - | - | 1.04 | - | ||||
American Kestrel | Falco sparverius | Not reported | 0.6 mg/kg | IM | Kestrels were fed killed, previously frozen mice or day-old chicks and had ad libitum access to water | - | 242.9 | 94.9 | 1.54 | - | [42,43,44,45,46] |
Not reported | 0.6 mg/kg | Intravenous | - | - | - | 1.76 | - | ||||
Not reported | 1.8 mg/kg | IM | Sustained release | 69.2 | - | 11.1 | - | ||||
Not reported | 1.8 mg/kg | SC | Sustained release | 72.3 | - | 13.5 | - | ||||
Red-tailed Hawk | Buteo jamaicensis | 1.28 kg | 0.3 mg/kg | SC | Food withheld 12 h prior to administration and normal feeding schedule resume 24 h after administration | Concentrated | 74.1 ± 37.0 | - | 6.23 ± 0.31 | - | [46,47] |
1.28 kg | 1.8 mg/kg | SC | Concentrated | 322.1 ± 57.7 | - | 7.84 ± 3.29 | - | ||||
Cockatiel | Nymphicus hollandicus | 106 ± 19.6 g | 0.6 mg/kg | IM | - | - | 240 ± 44.3 | - | 2.31 | - | [48] |
BUTORPHANOL | |||||||||||
Hispaniolan Parrot | Amazona ventralis | 289 g | 5 mg/kg | Oral | Fed a commercially available pelleted diet ad libitum and had constant access to water | - | - | 5.90 | - | - | [49,50,51,52] |
289 g | 5 mg/kg | IM | - | 653.42 | 130 | 0.51 | - | ||||
289 g | 5 mg/kg | Intravenous | - | - | - | 0.49 | - | ||||
305.5 ± 18 g | 12.5 mg/kg | SC | Long-acting poloxamer gel | 452.3 ± 78.0 | - | 3.41 ± 3.44 | - | ||||
Great Horned Owl | Bubo virginianus | 940 to 1450 g | 0.5 mg/kg | Intravenous to right jugular vein | - | - | - | - | 1.79 ± 1.36 | - | [53] |
940 to 1450 g | 0.5 mg/kg | Intravenous tp pectoral muscle | - | - | 1.19 ± 0.34 | - | |||||
940 to 1450 g | 0.5 mg/kg | Intramuscular | - | - | 229.9 ± 109.7 | - | 1.84 ± 1.56 | - | |||
Red-tailed Hawk | Buteo jamaicensis | 940 to 1450 g | 0.5 mg/kg | Intravenous to right jugular vein | - | - | - | - | 0.94 ± 0.30 | - | [53] |
940 to 1450 g | 0.5 mg/kg | Intramuscular | - | - | 154.4 ± 70.0 | - | 0.94 ± 0.26 | - | |||
Broiler Chicken | - | 2 kg | 2 mg/kg | Intravenous | They were fed ad libitum with commercial broiler feed and had access to fresh clean water. | - | - | - | 1.16 | - | [55] |
American Kestrel | Falco sparverius | 108.4 ± 6.4 g | 6 mg/kg | Intramuscular | They were fed frozen-thawed, medium-sized mice and provided water ad libitum | - | 445 | 1.48 | - | [54] | |
FENTANYL | |||||||||||
Chickens (Delaware, Redstar and Wyandotte) | - | 2.20–3.46 kg | 25 μg/h for 30 s | Transdermal | Birds were fed routine diet, including daily free-choice of grain, varied seasonal produce, and water. | - | 2.86 ± 2.58 | - | 7.1 ± 4.9 | - | [59] |
Chickens (Brahma and Wyandotte) | - | 2.20–3.46 kg | 25 μg/h for 30 s | Transdermal | - | 2.86 ± 2.58 | - | 7.2 ± 3.7 | - | [59] | |
Helmeted Guineafowl | Numida meleagris | 1.38–1.94 kg | 5 mg/kg | Transdermal | Birds had ad libitum access to water and exotic gamebird maintenance. | Solution | 228.8 | - | 33.2 | - | [58] |
White Cockatoo | Cacatua alba | 572 ± 125 g | 0.01 | Intramuscular | Water and a pelleted diet were proviccded ad libitum | - | 2.23 ± 0.51 | - | 1.44 ± 0.45 | - | [57] |
572 ± 125 g | 0.02 | Intramuscular | - | 3.33 ± 1.06 | - | 1.16 ± 0.42 | - |
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Aliansyah, E.; Chng, H.T.; Xie, S. A Critical Review of the Pharmacokinetics and Pharmacodynamics of Opioid Medications Used in Avian Patients. Birds 2022, 3, 1-28. https://doi.org/10.3390/birds3010001
Aliansyah E, Chng HT, Xie S. A Critical Review of the Pharmacokinetics and Pharmacodynamics of Opioid Medications Used in Avian Patients. Birds. 2022; 3(1):1-28. https://doi.org/10.3390/birds3010001
Chicago/Turabian StyleAliansyah, Evelyn, Hui Ting Chng, and Shangzhe Xie. 2022. "A Critical Review of the Pharmacokinetics and Pharmacodynamics of Opioid Medications Used in Avian Patients" Birds 3, no. 1: 1-28. https://doi.org/10.3390/birds3010001