An analysis of patient-reported outcomes (PRO) in breast cancer patients through item-response theory (IRT) pharmacometric modeling

Aims: Patient-reported outcomes (PRO) provide a valuable means to assess the subjective impact of a disease and treatment on patients' symptoms, adverse effects...

Optimization of trial design and dose selection based on the quantitative assessment of the efficacy of TAK-385, an investigational, oral GnRH antagonist, in patients with prostate cancer

Aims: To select a dose for confirmatory trials using prospective simulations based on a PK/PD model of testosterone (T) suppression with the non-peptide gonadot...

Modeling tumor size and survival in patients with metastatic gastric cancer

Aims: The aim of this study is to 1) model the temporal course of tumor size of stage IV gastric cancer patients enrolled into 1st line chemotherapy trials, and...

Pharmacometric modelling of antimalarial drugs in development

Aims: Determination of minimum inhibitory concentration (MIC) of antimalarial drugs in the clinical setting may provide a valuable alternative to empirical appr...

Recommended doses of Levobupivacaine for TAP Blocks: Development of a pharmacokinetic model and estimation of the risk of symptoms of local anesthetic systemic toxicity

Aims: Tranversus Abdominal Plane (TAP) blocks are widely used for postoperative analgesia following abdominal surgery. In this block, the local anaesthetic (LA)...

Assessment of pharmacometric and statistical analysis methods in dose-finding trial design: application in diabetes drug development

Aims: To evaluate the performance of different pharmacometric and statistical methods of analysis when evaluating power of dose-finding trial designs for treatm...

Why MIC is poison for the mind

The cost of drug development has exploded in recent years and risen to a level that soon will no longer be affordable to society. One reason for the high cost o...

A simple mechanistic pharmacometric model for HIV in children and adults

Aims: Models for CD4 count and viral load have long been crucial in antiretroviral drug development [1], and have increasingly been used in long-term pharmacome...

Population pharmacokinetics and pharmacodynamics of an oral glucagon receptor antagonist (LY2409021) and implications of patient dropout

Aims: Study protocols for antidiabetic drugs often include withdrawing study participants due to elevated fasting plasma glucose (FPG) and glycosylated hemoglob...

The importance of body size for bridging studies

Clinical development standard in Japan has changed over the last decades along with ICH E5 and Japan guidelines (JP GLs; by MHLW, PMDA) that support use of non-...

Application of a quantitative systems pharmacology (QSP) model to evaluate xCT inhibition as a target for central nervous system diseases.

Application of a quantitative systems pharmacology (QSP) model to evaluate xCT inhibition as a target for central nervous system diseases.   Aims: Neuronal exci...

Big world challenges for pharmacometrics

Aims From the outset, the aim of pharmacometrics has been to improve patient therapy through model based methods. The focus of these efforts have shifted over t...

Amikacin pharmacokinetics in Pediatric patients with burn injuries compared to those with oncology conditions

Aims: Physiologic changes due to disease status can lead to highly variable pharmacokinetics (PK) of amikacin in children. Therefore, considerations should be g...

A Framework for quantifying the influence of adherence and dose individualization

Aims: The property of a drug that signifies the likelihood of therapeutic success to imperfect adherence is termed forgiveness. Recently forgiveness has been qu...

Mechanism-based modelling to assess suppression of bacterial resistance by high intensity, short duration tobramycin exposure

  Aims: Infections involving hypermutable Pseudomonas aeruginosa (Pa) are highly problematic due to their enhanced resistance emergence. For aminoglycosides suc...

Quantitative Review and Meta-models of Gastrointestinal Transit Times to Help Inform Mechanistic Oral Absorption Models

Aims: The in vivo performance of single-unit ("tablet/capsule") and multiple-units ("pellets, multi-tablets") dosage forms may sometime be markedly influenced b...

Quantitative Review and Meta-models of Gastrointestinal pH to Help Inform Mechanistic Oral Absorption Models

Aims: The oral bioavailability of drugs is influenced by a many factors including the regional gastrointestinal (GI) pH. Small changes in the GI pH profile may ...

The population pharmacokinetics of OZ439 in healthy volunteers and patients with falciparum and vivax malaria

Aims: Artemisinin-based combination therapies are the recommended first-line treatment for falciparum malaria. Artemisinin derivatives, containing the peroxide ...

Tofacitinib Pharmacokinetics in Moderate-to-Severe Crohn’s Disease Patients in Phase 2 Induction and Maintenance Studies

Aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for inflammatory bowel disease. The aims of this analysis were to...

Population of Pharmacokinetics of Tanezumab in Pateints with Chronic Low Back Pain

Aims: Tanezumab is a monoclonal lgG antibody targeted against nerve growth factor (NGF). It is currently under clinical development for the treatment of chronic...

Examining the predictive performance of different equations to estimate glomerular filtration rate in paediatric oncology patients.

Aims: The National Kidney Foundation guidelines recommend the use of equations to estimate glomerular filtration rate (GFR) in paediatrics and adults, some of w...

Population pharmacokinetic model of gentamicin in paediatric oncology patients.

Aims: To describe the population pharmacokinetics of gentamicin in paediatric febrile neutropenic patients and to identify covariates which explain pharmacokine...

Evaluation of intraocular penetration of levofloxacin after administration drop solution by high performance liquid chromatography and comparison with ciprofloxacin

Introduction: Levofloxacin is used to treat a wide variety of bacterial infections. Levofloxacin belongs to a class of drugs called quinolone antibiotics. It wo...

Population pharmacokinetic model of pegylated interferon alfa-2a in healthy Korean male subjects

Aims: Pegylated interferon alfa-2a is an antiviral drug approved for the treatment of chronic hepatitic B and C. The addition of polyethylene glycol (pegylation...

Would a certification process for models published on the DDMoRe repository serve the modelling community?

Aims: The Drug Disease Model Resources (DDMoRe, http://www.ddmore.eu/) consortium was created to improve the quality, efficiency and cost effectiveness of Model...

An optimal sampling schedule for neonates, infants & children receiving cefazolin +/- vancomycin for cardiopulmonary bypass

Background: Dosing of prophylactic antibiotics in children during cardiopulmonary bypass (CPB) remains poorly defined. Pharmacokinetic (PK) studies can be impro...

Pseudomonas aeruginosa eradication therapy predicts the hazard of having Aspergillus Fumigatus positive culture in early life of children with CF

Aims: To describe the hazard of having Aspergillus fumigatus positive cultures in young children (≤ 5 years of age) with cystic fibrosis (CF) and to investigate...

How can users benefit from the DDMoRe common language standard and interoperability framework?

Aims: DDMoRe is a consortium of European Federation of Pharmaceutical Industries and Associations (EFPIA), Academic and Small Medium Enterprise (SME) partners f...

A Quantitative Systems Pharmacology Model to Predict the Effects of Warfarin, Rivaroxaban and Enoxaparin on the Human Coagulation Network

Aims: Warfarin is the anticoagulant of choice for venous thromboembolism treatment. However, its suppression of the endogenous clot dissolution components PC an...

Faster ADVAN-style analytical solutions for simulations from common pharmacokinetic models

Aims: ADVAN-style analytical solutions for 1, 2, 3 compartment linear pharmacokinetic models of intravenous bolus, infusion, and first-order absorption have bee...

A population model for respiratory syncytial virus (RSV) kinetics using transit compartments based on human challenge data

Aims: Respiratory syncytial virus (RSV) causes acute respiratory tract infections, and is a major cause of hospital admissions and death in young children world...

Model-Based Meta-Analysis on the Efficacy of Pharmacological Treatments for Idiopathic Pulmonary Fibrosis

Aims: Recently the FDA approved the first two drugs (pirfenidone and nintedanib) indicated for the treatment of idiopathic pulmonary fibrosis (IPF), a therapeut...

When statistics and pharmacometrics join forces for advanced quantitative drug development: A case study

Aims: The design of full development trials requires a number of features to be defined. Those include the population, treatment regimen, endpoint with clinical...

What purpose is the DDMoRe library serving?

DDMoRe, Drug Disease Model Resources, (http://www.ddmore.eu/) is an European project founded by the IMI and EFPIA, which aims to improve efficiency in the proce...

Population Pharmacokinetics of Artesunate and Dihydroartemisinin in Patients with Sensitive and Resistant Malaria Infection

Aims: Artemisinin-resistant falciparum malaria is now prevalent in Southeast Asia. Understanding the pharmacokinetic and pharmacodynamic properties of artesunat...

Pharmacokinetic Modeling and Simulation Analysis of LCB01-0371, a New Oxazolidinone Antibiotic Under Clinical Development

Aims: LCB01-0371 is a new oxazolidinone antibiotic with cyclic amidrazone under clinical development. It exerts its anti-bacterial activity by binding to bacter...

A simulation study to evaluate treatment effect of tamoxifen by CYP2D6 genotypes compared with AIs

Aims: Tamoxifen is a prodrug, and active metabolites including endoxifen are known to exert its therapeutic effect of tamoxifen. Tamoxifen is converted to endox...

Population Plasma and Urine Pharmacokinetics of Ivabradine and its Active Metabolite in Korean Healthy Volunteers

Aims: Ivabradine, a selective inhibitor of the pacemaker current (If), is used for heart failure and coronary heart disease, and mainly metabolized to S18982 (1...

Pharmacokinetic and Pharmacodynamic Modeling and Simulation Analysis of A Novel Donepezil Patch Formulation

Aims: Donepezil is a well-known reversible noncompetitive acetylcholinesterase inhibitor for the symptomatic treatment of Alzheimer's disease (AD). The purpose ...

Physiologically Based Pharmacokinetic Models for Trastuzumab Using Serial Concentrations Meausred By Optical Imaging in Mouse

Aims: Trastuzumab is a monoclonal antibody that is mainly used to treat breast cancer and exerts its therapeutic effect by inhibiting the HER2/neu receptor. The...

Pharmacokinetic and Pharmacodynamic Analysis of GCC-4401C, a Novel Direct Factor Xa Inhibitor, in Healthy Volunteers

Aims: GCC-4401C, an orally active direct factor Xa inhibitor which is similar to rivaroxaban, is currently under development for venous thromboembolic disease. ...

Simulation Analysis to Explore the Optimal Combination of Pregabalin and Duloxetine

Aims: Pregabalin, an anticonvulsant drug and duloxetine, a selective serotonin-norepinephrine reuptake inhibitor (SNRI) are used for pain relief. The purpose of...

Internal Deterministic Identifiability

Aims: Identifiability is an important component of model development. An identifiability analysis can provide the basis for understanding the limits of model st...

Mechanistic model for calcium treatment effect in calcium-parathyroid hormone homeostasis after thyroidectomy in Koreans.

Aims: This study aims to develop a mechanism-based model of calcium treatment effect in calcium-parathyroid hormone (PTH) homeostasis after thyroidectomy in Kor...

Development of a Biomarker-based Prediction Model of Disease Progression during Chemotherapy in Young Adolescents

Aims: This study aims to develop a quantitative semi-mechanistic model to describe the disease progression of leukemia during chemotherapy using circulating bio...

Advanced methods for dose finding during drug development: Summary of the EMA /EFPIA workshop on dose finding (London 4-5 December 2014)

Aims: The most commonly used methods for defining the dose rationale during early stage drug development i.e. pairwise comparison of different doses have shown ...

How Pharmacometrics can improve the power of pharmacogenetic studies

Aims: Pharmacogenetics (PG) studies the relationship between genetic variation and drug response with the aim of providing more precision to the development of ...

A viral kinetic model for severe human cytomegalovirus infections in immunocompromised paediatric patients

Aims: To produce a viral kinetic (VK) model of Cytomegalovirus (CMV) that predicts changes in viral load within an individual as the infection responds to antiv...

Bayesian forecasting versus clinical practice for intravenous busulfan dose adjustment in paediatric stem cell transplantations

Aims: Haematopoietic stem cell transplantation (HSCT) is a vital therapy that is used to cure high-risk or relapsed malignant and nonmalignant conditions. Busul...

Population modelling of functional disability in early rheumatoid arthritis treated according to a treat-to-target strategy

Aims: The treat-to-target approach in the management of rheumatoid arthritis (RA) involves frequent assessments of disease activity (measured by the 28-joint di...

Comparison of non-compartmental analysis and non-linear mixed effects ability to determine bioequivalence in drugs with two-compartment kinetics

Aims: To develop a software tool with the ability to rapidly compare Non-Compartmental Analysis (NCA) and Non-Linear Mixed-Effect Modelling (NLMEM) methods in d...

nlmixr: an open-source package for pharmacometric modelling in R

Aims: nlmixr is an open-source R package under development that builds on both RxODE1, an R package for simulation of nonlinear mixed effect models using ordina...

Population Pharmacokinetic Analysis of Levetiracetam in Adult Malaysian Patients with Epilepsy

Aims: To determine the pharmacokinetic parameters of levetiracetam (LEV), a third-generation antiepileptic drug, and its metabolite, etiracetam carboxylic acid ...

Pharmacometric modelling of antimalarial drugs in development: from challenge to clinics

Aims: guide the dose finding in clinical studies based on the Induced Blood Stage Malaria (IBSM) challenge studies and population pharmacokinetic-pharmacodynami...

Prediction of fat free mass in children

Aims: Fat free mass (FFM) describes the non-fat component of the body. It has been advocated as an appropriate size descriptor to scale drug clearance (CL) and ...

Understanding the influence of vitamin K on warfarin dosing requirements

Aims: Warfarin acts by inhibiting the reduction of vitamin K (VK) to its active form, thereby decreasing the production of VK-dependent coagulation factors. The...

Dose selection for rifabutin in combination with HIV-protease inhibitors

  Aims: Extensive but fragmented data from existing studies were used to describe the drug-drug interaction between rifabutin and HIV-protease inhibitors, and p...

Understanding Identifiability of random effects in mixed effects models

Aims: We discuss the question of model identifiability within the context of nonlinear mixed effects models and application to pharmacokinetic models. Methods: ...

Quantitative model diagrams (QMD): a new perspective in model evaluation

Aims: To facilitate model communication and evaluation through intuitive visual representation of their structure, parameter values and uncertainty. Methods: An...

A pilot study to investigate the relationship between doxorubicin and doxorubicinol pharmacokinetics and cardiotoxicity in children and adolescents with cancer

Aims: The primary aim of this pilot study was to assess the relationship between doxorubicin (dox) and doxorubicinol (doxinol) pharmacokinetics (PK) and markers...

Using normal fat mass to account for body size and composition

Aims:    Allometry is the study of how body size is related to body function. In clinical medicine, size related differences in biological functions such as hea...