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Evaluation of novel formulations of d-ß-hydroxybutyrate and melatonin in a rat model of hemorrhagic shock.
Wolf, Andrea; Thakral, Seema; Mulier, Kristine E; Suryanarayanan, Raj; Beilman, Gregory J.
Afiliação
  • Wolf A; Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: awolf@umn.edu.
  • Thakral S; Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.
  • Mulier KE; Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
  • Suryanarayanan R; Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.
  • Beilman GJ; Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
Int J Pharm ; 548(1): 104-112, 2018 Sep 05.
Article em En | MEDLINE | ID: mdl-29936200
d-ß-hydroxybutyrate and melatonin (BHB/MLT) infusion improves survival in hemorrhagic shock models. The original BHB/MLT formulation contains dimethyl sulfoxide (DMSO) to increase melatonin solubility. We formulated BHB/MLT solutions wherein DMSO was replaced either with 10% polyvinylpyrrolidone (BHB/MLT/PVP) or with 5% hydroxypropyl-ß-cyclodextrin/2.5% PVP/2.5% polyethylene glycol 400 (BHB/MLT/CD). Safety and efficacy of the new and the original BHB/MLT solution were tested in a lethal rat hemorrhagic shock model, with seven groups: 1) sham, 2) shock, untreated, 3) shock, lactated Ringer's solution (LR), 4) shock, 4 M BHB/MLT/DMSO, 5) shock, 2 M BHB/MLT/DMSO, 6) shock, BHB/MLT/PVP and 7) shock, BHB/MLT/CD. BHB/MLT/DMSO was given at full strength and 1:1 dilution to match the concentration of the novel formulations. Rats were anesthetized, instrumented, and 40% of the total blood volume was withdrawn in three steps, followed by four-hour long shock. Treatment boluses were infused half-way throughout hemorrhage. Survival was highest in BHB/MLT/CD-treated rats (8/10), followed by the BHB/MLT/PVP (6/10), 4 M BHB/MLT/DMSO (5/10) or 2 M BHB/MLT/DMSO (5/10), LR (3/10) and the untreated group (0/11). Survival did not differ significantly between BHB/MLT groups (p > 0.05), but was significantly higher in BHB/MLT/CD than in LR-treated animals (p = 0.018). BHB/MLT/PVP and BHB/MLT/CD constitute promising candidates for clinical hemorrhagic shock treatment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Choque Hemorrágico / Ácido 3-Hidroxibutírico / Melatonina Limite: Animals Idioma: En Revista: Int J Pharm Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Choque Hemorrágico / Ácido 3-Hidroxibutírico / Melatonina Limite: Animals Idioma: En Revista: Int J Pharm Ano de publicação: 2018 Tipo de documento: Article