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Innovative Approaches to Optimize Clinical Transporter Drug-Drug Interaction Studies.
Paglialunga, Sabina; Benrimoh, Natacha; van Haarst, Aernout.
Afiliação
  • Paglialunga S; Scientific Affairs, Celerion, Tempe, AZ 85283, USA.
  • Benrimoh N; Data Management and Biometrics, Celerion, Montreal, QC H4M 2N8, Canada.
  • van Haarst A; Scientific Affairs, Celerion, Belfast BT9 6AD, UK.
Pharmaceutics ; 16(8)2024 Jul 26.
Article em En | MEDLINE | ID: mdl-39204337
ABSTRACT
Of the 450 cell membrane transporters responsible for shuttling substrates, nutrients, hormones, neurotransmitters, antioxidants, and signaling molecules, approximately nine are associated with clinically relevant drug-drug interactions (DDIs) due to their role in drug and metabolite transport. Therefore, a clinical study evaluating potential transporter DDIs is recommended if an investigational product is intestinally absorbed, undergoes renal or hepatic elimination, or is suspected to either be a transporter substrate or perpetrator. However, many of the transporter substrates and inhibitors administered during a DDI study also affect cytochrome P450 (CYP) activity, which can complicate data interpretation. To overcome these challenges, the assessment of endogenous biomarkers can help elucidate the mechanism of complex DDIs when multiple transporters or CYPs may be involved. This perspective article will highlight how creative study designs are currently being utilized to address complex transporter DDIs and the role of physiology-based -pharmacokinetic (PBPK) models can play.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceutics Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceutics Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos