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Article
Open AccessSignificant impact of time-of-day variation on metformin pharmacokinetics
The objective was to investigate if metformin pharmacokinetics is modulated by time-of-day in humans using empirical and mechanistic pharmacokinetic modelling techniques on a large clinical dataset. This study...
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Article
Open AccessA Comprehensive Whole-Body Physiologically Based Pharmacokinetic Drug–Drug–Gene Interaction Model of Metformin and Cimetidine in Healthy Adults and Renally Impaired Individuals
Metformin is a widely prescribed antidiabetic BCS Class III drug (low permeability) that depends on active transport for its absorption and disposition. It is recommended by the US Food and Drug Administration...
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Article
Open AccessEffective Removal of Dabigatran by Idarucizumab or Hemodialysis: A Physiologically Based Pharmacokinetic Modeling Analysis
Application of idarucizumab and hemodialysis are options to reverse the action of the oral anticoagulant dabigatran in emergency situations.
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Article
A Comprehensive Whole-Body Physiologically Based Pharmacokinetic Model of Dabigatran Etexilate, Dabigatran and Dabigatran Glucuronide in Healthy Adults and Renally Impaired Patients
The thrombin inhibitor dabigatran is administered as the prodrug dabigatran etexilate, which is a substrate of esterases and P-glycoprotein (P-gp). Dabigatran is eliminated via renal excretion but is also a su...
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Article
Open AccessPhysiologically Based Pharmacokinetic Models for Prediction of Complex CYP2C8 and OATP1B1 (SLCO1B1) Drug–Drug–Gene Interactions: A Modeling Network of Gemfibrozil, Repaglinide, Pioglitazone, Rifampicin, Clarithromycin and Itraconazole
Drug–drug interactions (DDIs) and drug–gene interactions (DGIs) pose a serious health risk that can be avoided by dose adaptation. These interactions are investigated in strictly controlled setups, quantifying...
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Article
A physiologically based pharmacokinetic (PBPK) parent-metabolite model of the chemotherapeutic zoptarelin doxorubicin—integration of in vitro results, Phase I and Phase II data and model application for drug–drug interaction potential analysis
Zoptarelin doxorubicin is a fusion molecule of the chemotherapeutic doxorubicin and a luteinizing hormone-releasing hormone receptor (LHRHR) agonist, designed for drug targeting to LHRHR positive tumors. The a...