Utilising Endogenous Biomarkers in Drug Development to Streamline the Assessment of Drug-Drug Interactions Mediated by Renal Transporters: A Pharmaceutical Industry Perspective.
Clin Pharmacokinet
; 63(6): 735-749, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38867094
ABSTRACT
The renal secretion of many drugs is facilitated by membrane transporters, including organic cation transporter 2, multidrug and toxin extrusion protein 1/2-K and organic anion transporters 1 and 3. Inhibition of these transporters can reduce renal excretion of drugs and thereby pose a safety risk. Assessing the risk of inhibition of these membrane transporters by investigational drugs remains a key focus in the evaluation of drug-drug interactions (DDIs). Current methods to predict DDI risk are based on generating in vitro data followed by a clinical assessment using a recommended exogenous probe substrate for the individual drug transporter. More recently, monitoring plasma-based and urine-based endogenous biomarkers to predict transporter-mediated DDIs in early phase I studies represents a promising approach to facilitate, improve and potentially avoid conventional clinical DDI studies. This perspective reviews the evidence for use of these endogenous biomarkers in the assessment of renal transporter-mediated DDI, evaluates how endogenous biomarkers may help to expand the DDI assessment toolkit and offers some potential knowledge gaps. A conceptual framework for assessment that may complement the current paradigm of predicting the potential for renal transporter-mediated DDIs is outlined.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Membrana Transportadoras
/
Biomarcadores
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Interações Medicamentosas
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Desenvolvimento de Medicamentos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Clin Pharmacokinet
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Clin. pharmacokinetics
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Clinical pharmacokinetics
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos