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Article
Open AccessEntrectinib dose confirmation in pediatric oncology patients: pharmacokinetic considerations
Entrectinib is a central nervous system-active potent inhibitor of tropomyosin receptor kinase (TRK), with anti-tumor activity against neurotrophic NTRK gene fusion-positive tumors. This study investigates the ph...
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Article
Open AccessCombined Semi-mechanistic Target-Mediated Drug Disposition and Pharmacokinetic–Pharmacodynamic Models of Alirocumab, PCSK9, and Low-Density Lipoprotein Cholesterol in a Pooled Analysis of Randomized Phase I/II/III Studies
Alirocumab is a cholesterol-lowering monoclonal antibody targeting proprotein convertase subtilisin kexin type 9 (PCSK9) indicated in the prevention of cardiovascular risk and exhibiting target-mediated drug d...
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Article
Efficacy and safety exposure–response analyses of entrectinib in patients with advanced or metastatic solid tumors
Entrectinib is an anti-cancer agent that inhibits TRKA/B/C, ROS1, and ALK. Secondary pharmacokinetic (PK) exposure parameters for entrectinib derived from a previously described population PK model were used t...
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Article
Open AccessIn vitro and clinical investigations to determine the drug-drug interaction potential of entrectinib, a small molecule inhibitor of neurotrophic tyrosine receptor kinase (NTRK)
Background Entrectinib is a CNS-active, potent inhibitor of tyrosine receptor kinases A/B/C, ROS1 and anaplastic lymphoma kinase approved for use in patients with solid tumors. We describe the in vitro and clinic...
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Article
Population pharmacokinetic analysis of entrectinib in pediatric and adult patients with advanced/metastatic solid tumors: support of new drug application submission
Entrectinib (ROZLYTREK®) is a CNS-active, potent, and selective inhibitor of ROS1, TRK A/B/C, and ALK kinase activity. It was recently approved for the treatment of ROS1-positive non-small cell lung cancer and NT...
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Article
Physiologically-Based Pharmacokinetic Modelling of Entrectinib Parent and Active Metabolite to Support Regulatory Decision-Making
Entrectinib is a selective inhibitor of ROS1/TRK/ALK kinases, recently approved for oncology indications. Entrectinib is predominantly cleared by cytochrome P450 (CYP) 3A4, and modulation of CYP3A enzyme activ...
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Article
Population Pharmacokinetics and Pharmacodynamics of Meropenem in Critically Ill Patients: How to Achieve Best Dosage Regimen According to the Clinical Situation
Meropenem is frequently used for the treatment of severe bacterial infections in critically ill patients. Because critically ill patients are more prone to pharmacokinetic variability than other patients, ensu...
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Open AccessCharacterization of the pharmacokinetics of entrectinib and its active M5 metabolite in healthy volunteers and patients with solid tumors
Background: Entrectinib is an oral, CNS-active, potent inhibitor of tyrosine receptor kinases A/B/C, tyrosine kinase ROS proto-oncogene 1, and anaplastic lymphoma kinase approved for use in patients with solid tu...
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Article
Physiologically Based Absorption Modelling to Explore the Impact of Food and Gastric pH Changes on the Pharmacokinetics of Entrectinib
Entrectinib is a potent and selective tyrosine kinase inhibitor (TKI) of TRKA/B/C, ROS1, and ALK with both systemic and CNS activities, which has recently received FDA approval for ROS1 fusion-positive non-sma...
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Article
Open AccessPopulation Pharmacokinetic/Pharmacodynamic Analysis of Alirocumab in Healthy Volunteers or Hypercholesterolemic Subjects Using an Indirect Response Model to Predict Low-Density Lipoprotein Cholesterol Lowering: Support for a Biologics License Application Submission: Part II
Alirocumab, a human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly lowers low-density lipoprotein cholesterol levels.
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Article
Open AccessTarget-Mediated Drug Disposition Population Pharmacokinetics Model of Alirocumab in Healthy Volunteers and Patients: Pooled Analysis of Randomized Phase I/II/III Studies
Proprotein convertase subtilisin/kexin type 9 inhibition with monoclonal antibodies such as alirocumab significantly reduces low-density lipoprotein-cholesterol levels ± other lipid-lowering therapies. We aime...
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Article
Open AccessOcular Drug Distribution After Topical Administration: Population Pharmacokinetic Model in Rabbits
When eye diseases are treated by topical administration, the success of treatment lies in the effective drug concentration in the target tissue. This is why the drug’s pharmacokinetic, in the different substru...
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Article
Sirolimus Population Pharmacokinetic/Pharmacogenetic Analysis and Bayesian Modelling in Kidney Transplant Recipients
Objectives: The objectives of the present study were: (i) to analyse the population pharmacokinetics of sirolimus in renal transplant recipients co-administered mycophenolate mofetil, but no calc...
