title: Pharmacokinetics of 2 formulations of buprenorphine in macaques (Macaca mulatta and Macaca fascicularis).
abstract: Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the tested doses. The low and high doses of buprenorphine had elimination half-lives of 2.6 ± 0.7 and 5.3 ± 2.0 h, respectively, but the low-dose data were constrained by the sensitivity of the analytical method. Sustained-release buprenorphine had an elimination half-life of 42.6 ± 26.2 h. The AUC0-Tlast of buprenorphine were 9.1 ± 4.3 and 39.0 ± 25.1 ng × h/mL for the low and high doses, respectively, and sustained-release buprenorphine had an AUC0-Tlast of 177 ± 74 ng × h/mL. Assuming a hypothesized therapeutic buprenorphine plasma concentration threshold of 0.1 ng/mL in macaques, these results suggest that buprenorphine doses of 0.01 mg/kg IM should be administered every 6 to 8 h, whereas doses of 0.03 mg/kg IM can be administered every 12 h. These results further demonstrate that a single 0.2-mg/kg SC injection of sustained-release buprenorphine maintains plasma concentrations above 0.1 ng/mL for 5 d in macaques. These findings support a new dosing strategy using sustained-release buprenorphine to improve pain management, decrease animal stress, improve animal welfare, and simplify the postoperative management of nonhuman primates in laboratory animal and zoological settings.
authors.affiliation: Biologic Resources Laboratory, University of Illinois at Chicago, Chicago, Illinois, USA. enunamak@uic.edu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Nunamaker
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Halliday
authors.forename: David E
authors.initials: DE
authors.lastname: Moody
authors.forename: Wenfang B
authors.initials: WB
authors.lastname: Fang
authors.forename: Matthew
authors.initials: M
authors.lastname: Lindeblad
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Fortman
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000827:Animal Welfare; D000818:Animals; D000830:Animals, Laboratory; D002047:Buprenorphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D003692:Delayed-Action Preparations; D007273:Injections, Intramuscular; D008252:Macaca fascicularis / Q000097:blood / Q000378:metabolism*; D008253:Macaca mulatta / Q000097:blood / Q000378:metabolism*; D008297:Male; D053719:Tandem Mass Spectrometry
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D002047:Buprenorphine
references.citation: Ther Drug Monit. 2006 Apr;28(2):245-51
references.pmid: 16628138
references.citation: Drug Metab Dispos. 2002 Dec;30(12):1478-83
references.pmid: 12433822
references.citation: J Am Assoc Lab Anim Sci. 2011 May;50(3):389-95
references.pmid: 21640036
references.citation: Am J Vet Res. 2011 Apr;72(4):461-6
references.pmid: 21453146
references.citation: J Vet Pharmacol Ther. 2009 Oct;32(5):503-5
references.pmid: 19754919
references.citation: Pain. 1985 Apr;21(4):315-327
references.pmid: 3923417
references.citation: J Vet Pharmacol Ther. 2007 Jun;30(3):249-56
references.pmid: 17472657
references.citation: Vet Clin North Am Exot Anim Pract. 2011 Jan;14(1):1-20
references.pmid: 21074699
references.citation: Vet Ther. 2008 Summer;9(2):83-93
references.pmid: 18597246
references.citation: Psychopharmacology (Berl). 2011 Aug;216(4):511-23
references.pmid: 21404039
references.citation: Eur J Drug Metab Pharmacokinet. 1980;5(4):233-9
references.pmid: 7250147
references.citation: Drug Metab Dispos. 1998 Aug;26(8):818-21
references.pmid: 9698298
references.citation: J Am Assoc Lab Anim Sci. 2010 Nov;49(6):805-8
references.pmid: 21205444
references.citation: J Pharmacol Exp Ther. 2009 Jul;330(1):135-41
references.pmid: 19351868
references.citation: J Am Vet Med Assoc. 1996 Sep 1;209(5):918-21
references.pmid: 8790540
references.citation: J Pharm Sci. 1985 May;74(5):515-24
references.pmid: 4020627
references.citation: J Vet Pharmacol Ther. 2005 Oct;28(5):453-60
references.pmid: 16207308
references.citation: J Am Assoc Lab Anim Sci. 2007 May;46(3):24-31
references.pmid: 17487949
references.citation: Drug Metab Dispos. 1995 Nov;23(11):1231-41
references.pmid: 8591724
references.citation: Curr Drug Metab. 2009 Mar;10(3):236-46
references.pmid: 19442086
references.citation: Life Sci. 1997;60(22):1953-64
references.pmid: 9180349
references.citation: Neurotoxicol Teratol. 1993 Mar-Apr;15(2):145-9
references.pmid: 8510609
references.citation: Br J Pharmacol. 2009 Jul;157(6):907-21
references.pmid: 19508398
references.citation: Br J Pharmacol. 1987 Nov;92(3):527-33
references.pmid: 3427266
references.citation: Lab Anim. 2002 Jul;36(3):322-43
references.pmid: 12144743
references.citation: Drug Metab Dispos. 2001 Feb;29(2):121-6
references.pmid: 11159800
references.citation: Drug Metab Dispos. 2006 Sep;34(9):1502-7
references.pmid: 16763016
references.citation: Vet J. 2011 Mar;187(3):335-41
references.pmid: 20206560
references.citation: Drugs. 2003;63(19):1999-2010; discussion 2011-2
references.pmid: 12962515
references.citation: J Am Assoc Lab Anim Sci. 2011 Mar;50(2):198-204
references.pmid: 21439213
references.citation: Clin Ther. 2007 Aug;29(8):1620-31
references.pmid: 17919544
references.citation: Anesthesiology. 2011 Dec;115(6):1251-60
references.pmid: 22037640
references.citation: Epilepsia. 1979 Dec;20(6):623-33
references.pmid: 115675
references.citation: Drug Metab Dispos. 1984 Sep-Oct;12(5):577-81
references.pmid: 6149907
references.citation: Clin Ther. 2003 Jan;25(1):150-68
references.pmid: 12637117
references.citation: Drug Metab Dispos. 2002 Jul;30(7):853-8
references.pmid: 12065445
references.citation: J Vet Pharmacol Ther. 1997 Dec;20(6):453-63
references.pmid: 9430769
references.citation: J Pharm Sci. 1986 Nov;75(11):1028-40
references.pmid: 3820096
references.citation: J Vet Pharmacol Ther. 2012 Feb;35(1):52-8
references.pmid: 21392040
references.citation: Anal Biochem. 2002 Jul 1;306(1):31-9
references.pmid: 12069411
references.citation: J Am Vet Med Assoc. 2011 Feb 1;238(3):318-28
references.pmid: 21281215