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Pharmacokinetics and safety of inhaled ivermectin in mice as a potential COVID-19 treatment.
Albariqi, Ahmed H; Wang, Yuncheng; Chang, Rachel Yoon Kyung; Quan, Diana H; Wang, Xiaonan; Kalfas, Stefanie; Drago, John; Britton, Warwick J; Chan, Hak-Kim.
Afiliación
  • Albariqi AH; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia; The Department of Pharmaceutics, Faculty of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia.
  • Wang Y; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia.
  • Chang RYK; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia.
  • Quan DH; Tuberculosis Research Program at the Centenary Institute, The University of Sydney, NSW 2006, Australia.
  • Wang X; Tuberculosis Research Program at the Centenary Institute, The University of Sydney, NSW 2006, Australia.
  • Kalfas S; Florey Institute of Neuroscience and Mental Health, Melbourne, VIC 3052, Australia.
  • Drago J; Florey Institute of Neuroscience and Mental Health, Melbourne, VIC 3052, Australia; Department of Medicine, St Vincent's Hospital, University of Melbourne, VIC 3010, Australia.
  • Britton WJ; Tuberculosis Research Program at the Centenary Institute, The University of Sydney, NSW 2006, Australia; Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia.
  • Chan HK; Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, NSW 2006, Australia. Electronic address: kim.chan@sydney.edu.au.
Int J Pharm ; 619: 121688, 2022 May 10.
Article en En | MEDLINE | ID: mdl-35314278
Pharmacokinetic limitations associated with oral ivermectin may limit its success as a potential COVID-19 treatment based on in vitro experiments which demonstrate antiviral efficacy against SARS-CoV-2 at high concentrations. Targeted delivery to the lungs is a practical way to overcome these limitations and ensure the presence of a therapeutic concentration of the drug in a clinically critical site of viral pathology. In this study, the pharmacokinetics (PK) and safety of inhaled dry powders of ivermectin with lactose were investigated in healthy mice. Female BALB/c mice received ivermectin formulation by intratracheal administration at high (3.15 mg/kg) or low doses (2.04 mg/kg). Plasma, bronchoalveolar lavage fluid (BALF), lung, kidney, liver, and spleen were collected at predetermined time points up to 48 h and analyzed for PK. Histological evaluation of lungs was used to examine the safety of the formulation. Inhalation delivery of ivermectin formulation showed improved pharmacokinetic performance as it avoided protein binding encountered in systemic delivery and maintained a high exposure above the in vitro antiviral concentration in the respiratory tract for at least 24 h. The local toxicity was mild with less than 20% of the lung showing histological damage at 24 h, which resolved to 10% by 48 h.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tratamiento Farmacológico de COVID-19 Límite: Animals / Female / Humans Idioma: En Revista: Int J Pharm Año: 2022 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tratamiento Farmacológico de COVID-19 Límite: Animals / Female / Humans Idioma: En Revista: Int J Pharm Año: 2022 Tipo del documento: Article País de afiliación: Arabia Saudita Pais de publicación: Países Bajos