The Effects of Intramuscular Naloxone Dose on Mu Receptor Displacement of Carfentanil in Rhesus Monkeys
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. General Considerations
4.2. Subjects
4.3. Nonhuman Primate PET Imaging Studies
4.4. PET Data Analysis
4.5. Study Drugs
4.6. Plasma Naloxone Assay
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Monkey Naloxone Dose (mg/kg) | Monkey 1 | Monkey 2 | ||
---|---|---|---|---|
[11C]CFN PET | PK | [11C]CFN PET | PK | |
0.00 (baseline) | n = 1 | n = 1 | n = 2 | n = 1 |
0.06 | n = 2 | n = 1 | n = 2 | n = 1 |
0.14 | n = 2 | n = 1 | n = 1 | n = 1 |
0.28 | n = 1 | n = 1 | n = 1 | n = 1 |
Monkey Naloxone IM Dose (mg/kg) | Human Equivalent IM Dose (mg/kg) [14] | IM Dose to Average 60 kg Human (mg) |
---|---|---|
0.06 | 0.02 | 1.2 |
0.14 | 0.045 | 2.7 |
0.28 | 0.09 | 5.4 |
Dose of Naloxone mg/kg | Basal Ganglia Mean %-RO (± SD) | Thalamus Mean %-RO ± SD |
---|---|---|
0.06 | 56 ± 17 | 47 ± 23 |
0.14 | 74 ± 7 | 65 ± 9 |
0.28 | 76 ± 3 | 74 ± 4 |
Dose of Naloxone mg/kg | Mean Plasma Conc NLX ± SD [Range] (ng/mL) 30 min Post-IM 1 | Mean Plasma Conc NLX ± SD [Range] (ng/mL) 60 min Post-IM |
---|---|---|
0.06 | 4.6 ± 1.9 [3.3–5.9] | 2.3 ± 2.4 [0.7–4.0] |
0.14 | 16.8 ± 2.3 [15.1–18.4] | 8.1 ± 1.0 [7.4–8.8] |
0.28 | 43.4 ± 19.0 [30.0–56.8] | 23.2 ± 1.6 [22.0–24.3] |
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Scott, P.J.H.; Koeppe, R.A.; Shao, X.; Rodnick, M.E.; Sowa, A.R.; Henderson, B.D.; Stauff, J.; Sherman, P.S.; Arteaga, J.; Carlo, D.J.; et al. The Effects of Intramuscular Naloxone Dose on Mu Receptor Displacement of Carfentanil in Rhesus Monkeys. Molecules 2020, 25, 1360. https://doi.org/10.3390/molecules25061360
Scott PJH, Koeppe RA, Shao X, Rodnick ME, Sowa AR, Henderson BD, Stauff J, Sherman PS, Arteaga J, Carlo DJ, et al. The Effects of Intramuscular Naloxone Dose on Mu Receptor Displacement of Carfentanil in Rhesus Monkeys. Molecules. 2020; 25(6):1360. https://doi.org/10.3390/molecules25061360
Chicago/Turabian StyleScott, Peter J. H., Robert A. Koeppe, Xia Shao, Melissa E. Rodnick, Alexandra R. Sowa, Bradford D. Henderson, Jenelle Stauff, Phillip S. Sherman, Janna Arteaga, Dennis J. Carlo, and et al. 2020. "The Effects of Intramuscular Naloxone Dose on Mu Receptor Displacement of Carfentanil in Rhesus Monkeys" Molecules 25, no. 6: 1360. https://doi.org/10.3390/molecules25061360
APA StyleScott, P. J. H., Koeppe, R. A., Shao, X., Rodnick, M. E., Sowa, A. R., Henderson, B. D., Stauff, J., Sherman, P. S., Arteaga, J., Carlo, D. J., & Moss, R. B. (2020). The Effects of Intramuscular Naloxone Dose on Mu Receptor Displacement of Carfentanil in Rhesus Monkeys. Molecules, 25(6), 1360. https://doi.org/10.3390/molecules25061360