Drug-drug Interactions and QT Prolongation as a Commonly Assessed Cardiac Effect – Comprehensive Overview of Clinical Trials

Proarrhythmia assessment is one of the major concerns for regulatory bodies and pharmaceutical industry. ICH guidelines recommending preclinical tests have been established in attempt to eliminate the risk of drug-induced arrhythmias. However, in the clinic, arrhythmia occurrence is determined not only by the inherent property of a drug to block ion currents and disturb electrophysiological […]

Read More
Topics:

Prediction of Drug-drug Interactions Arising From CYP3A Induction Using a Physiologically-based Dynamic Model

Using physiologically-based pharmacokinetic modeling, we predicted the magnitude of drug-drug interactions (DDIs) for studies with rifampicin and seven CYP3A4 probe substrates administered i.v. (10 studies) or orally (19 studies). The results showed a tendency to underpredict the DDI magnitude when the victim drug was administered orally. Possible sources of inaccuracy were investigated systematically to determine […]

Read More
Topics:

Metformin and Cimetidine: Physiologically-based Pharmacokinetic Modeling to Investigate Transporter Mediated Drug-drug Interactions

Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically–based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney […]

Read More
Topics:

Metformin and cimetidine: Physiologically based pharmacokinetic modeling to investigate transporter mediated drug-drug interactions.

Metformin is used as a probe for OCT2 mediated transport when investigating possible DDIs with new chemical entities. The aim of the current study was to investigate the ability of physiologically-based pharmacokinetic (PBPK) models to simulate the effects of OCT and MATE inhibition by cimetidine on metformin kinetics. PBPK models were developed, incorporating mechanistic kidney and […]

Read More
Topics:
Learn More
LinkedIn