Your browser doesn't support javascript.
loading
The Effect of High Storage Temperature on the Stability and Efficacy of Lyophilized Tenecteplase.
Henkel, Emily; Vella, Rebecca; Fenning, Andrew.
Afiliação
  • Henkel E; Central Queensland University, School of Health, Medical and Applied Sciences, Rockhampton, Queensland, Australia.
  • Vella R; Central Queensland University, School of Health, Medical and Applied Sciences, Rockhampton, Queensland, Australia.
  • Fenning A; Central Queensland University, School of Health, Medical and Applied Sciences, Rockhampton, Queensland, Australia.
Prehosp Disaster Med ; 35(5): 501-507, 2020 Oct.
Article em En | MEDLINE | ID: mdl-32686630
INTRODUCTION: Tenecteplase is a thrombolytic protein drug used by paramedics, emergency responders, and critical care medical personnel for the prehospital treatment of blood clotting diseases. Minimizing the time between symptom onset and the initiation of thrombolytic treatment is important for reducing mortality and improving patient outcomes. However, the structure of protein drug molecules makes them susceptible to physical and chemical degradation that could potentially result in considerable adverse effects. In locations that experience extreme temperatures, lyophilized tenecteplase transported in emergency service vehicles (ESVs) may be subjected to conditions that exceed the manufacturer's recommendations, particularly when access to the ambulance station is limited. STUDY OBJECTIVE: This study evaluated the impact of heat exposure (based on temperatures experienced in an emergency vehicle during summer in a regional Australian city) on the stability and efficacy of lyophilized tenecteplase. METHODS: Vials containing 50mg lyophilized tenecteplase were stored at 4.0°C (39.2°F), 35.5°C (95.9°F), or 44.9°C (112.8°F) for a continuous period of eight hours prior to reconstitution. Stability and efficacy were determined through assessment of: optical clarity and pH; analyte concentration using UV spectrometry; percent protein monomer and single chain protein using size-exclusion chromatography; and in vitro bioactivity using whole blood clot weight and fibrin degradation product (D-dimer) development. RESULTS: Heat treatment, particularly at 44.9°C, was found to have the greatest impact on tenecteplase solubility; the amount of protein monomer and single chain protein lost (suggesting structural vulnerability); and the capacity for clot lysis in the form of decreased D-dimer production. Meanwhile, storage at 4.0°C preserved tenecteplase stability and in vitro bioactivity. CONCLUSION: The findings indicate that, in its lyophilized form, even relatively short exposure to high temperature can negatively affect tenecteplase stability and pharmacological efficacy. It is therefore important that measures are implemented to ensure the storage temperature is kept below 30.0°C (86.0°F), as recommended by manufacturers, and that repeated refrigeration-heat cycling is avoided. This will ensure drug administration provides more replicable thrombolysis upon reaching critical care facilities.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estabilidade de Medicamentos / Armazenamento de Medicamentos / Liofilização / Tenecteplase / Temperatura Alta Tipo de estudo: Guideline Limite: Humans País/Região como assunto: Oceania Idioma: En Revista: Prehosp Disaster Med Assunto da revista: MEDICINA DE EMERGENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Austrália País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Estabilidade de Medicamentos / Armazenamento de Medicamentos / Liofilização / Tenecteplase / Temperatura Alta Tipo de estudo: Guideline Limite: Humans País/Região como assunto: Oceania Idioma: En Revista: Prehosp Disaster Med Assunto da revista: MEDICINA DE EMERGENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Austrália País de publicação: Estados Unidos