Evaluation of an improved sustained-release buprenorphine formulation for use in mice

Jason R. Healy Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506.

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Jennifer L. Tonkin Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506.

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Stacey R. Kamarec Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506.

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Mitchell A. Saludes Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506.

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Sherif Y. Ibrahim Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506.

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Rae R. Matsumoto Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, WV 26506.

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Jeffrey H. Wimsatt Department of Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506.

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DOI:
https://doi.org/10.2460/ajvr.75.7.619
Volume/Issue:
Volume 75: Issue 7
Online Publication Date:
01 Jul 2014
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Abstract

Objective—To evaluate analgesic effects of an improved sustained-release buprenorphine (BUP-SR) formulation administered to mice.

Animals—36 male Swiss-Webster mice.

Procedures—Mice were assigned to each of 3 treatment groups (n = 12 mice/group). Treatments were administered SC (vehicle [control treatment], 1.5 mg of buprenorphine hydrochloride [BUP-HCl]/kg, and 1.5 mg of BUP-SR/kg). Mice were evaluated (total activity, gastrointestinal tract motility, respiratory rate, cataleptic behavior, and tall-flick and hot plate nociception tests) to determine behavioral and physiologic responses at 4, 24, and 48 hours after treatment administration. Body weight and respiratory rate were measured before and at each time point after treatment administration.

Results—SC administration of BUP-SR resulted in significant antinociception effects for 48 hours for the hot plate and tall-flick nociception tests without substantial adverse effects. Gastrointestinal tract motility and total activity were higher at 4 hours for mice receiving BUP-SR than for mice receiving the vehicle, but values were the same between these groups at 24 and 48 hours. The BUP-SR group had a lower respiratory rate than did the control group at all times after treatment administration. Mice treated with BUP-SR had no significant changes in body weight during the study, whereas mice treated with BUP-HCl had a significant decrease in body weight at 24 and 48 hours.

Conclusions and Clinical Relevance—BUP-SR administration resulted in antinociception effects for 48 hours. Results of this study indicated that the improved BUP-SR formulation could be safely administered SC and conferred superior analgesia, compared with that for BUP-HCl, in mice.

Abstract

Objective—To evaluate analgesic effects of an improved sustained-release buprenorphine (BUP-SR) formulation administered to mice.

Animals—36 male Swiss-Webster mice.

Procedures—Mice were assigned to each of 3 treatment groups (n = 12 mice/group). Treatments were administered SC (vehicle [control treatment], 1.5 mg of buprenorphine hydrochloride [BUP-HCl]/kg, and 1.5 mg of BUP-SR/kg). Mice were evaluated (total activity, gastrointestinal tract motility, respiratory rate, cataleptic behavior, and tall-flick and hot plate nociception tests) to determine behavioral and physiologic responses at 4, 24, and 48 hours after treatment administration. Body weight and respiratory rate were measured before and at each time point after treatment administration.

Results—SC administration of BUP-SR resulted in significant antinociception effects for 48 hours for the hot plate and tall-flick nociception tests without substantial adverse effects. Gastrointestinal tract motility and total activity were higher at 4 hours for mice receiving BUP-SR than for mice receiving the vehicle, but values were the same between these groups at 24 and 48 hours. The BUP-SR group had a lower respiratory rate than did the control group at all times after treatment administration. Mice treated with BUP-SR had no significant changes in body weight during the study, whereas mice treated with BUP-HCl had a significant decrease in body weight at 24 and 48 hours.

Conclusions and Clinical Relevance—BUP-SR administration resulted in antinociception effects for 48 hours. Results of this study indicated that the improved BUP-SR formulation could be safely administered SC and conferred superior analgesia, compared with that for BUP-HCl, in mice.

Contributor Notes

Ms. Tonkin's present address is Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.

Dr. Healy was supported by a diversity supplement from the National Institutes of Health (DA013583).

The authors thank Dr. Kristie Brock, Dr. Ying Huang, Amber Forrisi, and Brandi Underwood for technical assistance.

Address correspondence to Dr. Wimsatt (jwimsatt@hsc.wvu.edu).
Cover American Journal of Veterinary Research
American Journal of Veterinary Research
Publication Date:
01 Jul 2014

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