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Physiologically Based Pharmacokinetic Modelling of Cabotegravir Microarray Patches in Rats and Humans.
Kinvig, Hannah; Rajoli, Rajith K R; Pertinez, Henry; Vora, Lalitkumar K; Volpe-Zanutto, Fabiana; Donnelly, Ryan F; Rannard, Steve; Flexner, Charles; Siccardi, Marco; Owen, Andrew.
Afiliação
  • Kinvig H; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L7 3NY, UK.
  • Rajoli RKR; Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L7 3NY, UK.
  • Pertinez H; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L7 3NY, UK.
  • Vora LK; Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L7 3NY, UK.
  • Volpe-Zanutto F; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L7 3NY, UK.
  • Donnelly RF; Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L7 3NY, UK.
  • Rannard S; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
  • Flexner C; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
  • Siccardi M; School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
  • Owen A; Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L7 3NY, UK.
Pharmaceutics ; 15(12)2023 Nov 30.
Article em En | MEDLINE | ID: mdl-38140050
ABSTRACT
Microarray patches (MAPs) are currently under investigation as a self-administered, pain-free alternative used to achieve long-acting (LA) drug delivery. Cabotegravir is a potent antiretroviral that has demonstrated superior results over current pre-exposure prophylaxis (PrEP) regimens. This study aimed to apply physiologically based pharmacokinetic (PBPK) modelling to describe the pharmacokinetics of the dissolving bilayer MAP platform and predict the optimal dosing strategies for a once-weekly cabotegravir MAP. A mathematical description of a MAP was implemented into a PBPK model, and empirical models were utilised for parameter estimation. The intradermal PBPK model was verified against previously published in vivo rat data for intramuscular (IM) and MAP administration, and in vivo human data for the IM administration of LA cabotegravir. The verified model was utilised for the prediction of 300 mg, 150 mg and 75 mg once-weekly MAP administration in humans. Cabotegravir plasma concentrations >4 × protein-adjusted 90% inhibitory concentration (PA-IC90) (0.664 µg/mL) and >8 × PA-IC90 (1.33 µg/mL) were set as targets. The 75 mg, 150 mg and 300 mg once-weekly cabotegravir MAP regimens were predicted to sustain plasma concentrations >4 × PA-IC90, while the 300 mg and 150 mg regimens achieved plasma concentrations >8 × PA-IC90. These data demonstrate the potential for a once-weekly cabotegravir MAP using practical patch sizes for humans and inform the further development of cabotegravir MAPs for HIV PrEP.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceutics Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceutics Ano de publicação: 2023 Tipo de documento: Article