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Front. Vet. Sci. | doi: 10.3389/fvets.2018.00019

Pharmacokinetic and Histopathological Evaluation of 25% Poloxamer as a Slow Release Carrier for Morphine in a Rat Model

  • 1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, United States
  • 2Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, United States
  • 3Departments of Agricultural and Biological Engineering, Department of Agriculture and Biological Engineering, Purdue University, United States
  • 4Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, United States
  • 5Purdue Translational Pharmacology CTSI core facility, Purdue University, United States

The objectives of this study were to evaluate poloxamer as a slow release carrier for morphine (M) and potential tissue irritation after subcutaneous (SC) poloxamer-morphine (PM) injection in a rat model. Based on the result of a previous in vitro work, 25% poloxamer, with and without morphine, and saline were administered in 14 rats’ flanks. Blood for morphine concentrations was automatically sampled at multiple preprogrammed time points using the CulexTM unit for 48 hours. Skin tissues from the injection sites were harvested and evaluated for histopathological changes. Following M or PM administration, it was determined that the half-life (t½) was significantly longer in the PM (5.5 ±7.2 hr) than M (0.7± 0.8 hr) indicated a slow dissolution of poloxamer with morphine. The tmax was within 15 minutes and Cmax was approximately 3 times higher with M than with PM, reaching 716.8 (±153.7 ng/ml) of plasma morphine concentrations. There was no significant difference in total area under the curve and clearance of M vs PM. Histology inflammatory scores were similar between M, PM, and poloxamer but were significantly higher than saline control. We concluded that 25% poloxamer was capable of increasing the t½ of morphine, without a significant tissue irritation.

Keywords: Poloxamer, Morphine, slow release, pharmacokinetics, histopathology, Rats

Received: 03 Dec 2017; Accepted: 31 Jan 2018.

Edited by:

Nora Mestorino, National University of La Plata, Argentina

Reviewed by:

Ender Yarsan, Pharmacology and Toxicology, Turkey
Jean-Claude DESFONTIS, INRA UMR703 Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation de Nantes-Atlantique, France  

Copyright: © 2018 Sulimai, Ko, Jones-Hall, Weng, Deng, Breur and Knipp. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: DVM. Jeff C. Ko, College of Veterinary Medicine, Purdue University, Department of Veterinary Clinical Sciences, West Lafayette, United States, jcko@purdue.edu