Innovative Approaches to Optimize Clinical Transporter Drug-Drug Interaction Studies.
Pharmaceutics
; 16(8)2024 Jul 26.
Article
in 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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Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Pharmaceutics
Year:
2024
Document type:
Article
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