Modeling Fluconazole – a Case with Concentration-Dependent Liver:Plasma Partition Coefficient

Modeling Fluconazole – a Case with Concentration-Dependent Liver:Plasma Partition Coefficient

Authors: Fraczkiewicz G, Parrott N, Lukacova V, Bolger MB, Crison JR, Woltosz WS, Lavé T
Conference: AAPS
Keywords: ADMET, antifungal, candidiasis, fluconazole, meningitis, PBPK
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

Fluconazole is an antifungal agent widely used in the clinical setting   for the treatment of candidiasis and meningitis. It undergoes minimal metabolism and is excreted renally.

PBPK Modeling of Fluoxetine and its Metabolite Norfluoxetine: Prediction of the Extent of Their Involvement in Drug Interactions

PBPK Modeling of Fluoxetine and its Metabolite Norfluoxetine: Prediction of the Extent of Their Involvement in Drug Interactions

Authors: Fraczkiewicz G, Lukacova V, Parrott N, Bolger MB, Crison JR, Woltosz WS, Lavé T
Conference: AAPS
Keywords: ADMET, Cp-Time, DDIs, drug-drug interactions (DDIs), fluoxetine, norfluoxetine, PBPK, tissue:plasma
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

The aim of our study was to simulate the human pharmacokinetics of fluoxetine and its major metabolite, norfluoxetine, and predict the magnitude of their drug-drug interactions (DDIs) using physiologically…

In Silico Prediction of Aqueous Solubility: The Solubility Challenge

In Silico Prediction of Aqueous Solubility: The Solubility Challenge

Authors: Hewitt M, Cronin MT, Enoch SJ, Madden JC, Roberts DW, Dearden JC
Publication: J Chem Inf Model
Keywords: aqueous solubility, dissolution, in silico models, solubility
Software: ADMET Predictor®

The dissolution of a chemical into water is a process fundamental to both chemistry and biology. The persistence of a chemical within the environment and the effects of a chemical...

A Pharmacokinetic Simulation-Based Comparison Of Varying Adherence Rates For Paliperidone ER And Risperidone In Patients With Schizophrenia

A Pharmacokinetic Simulation-Based Comparison Of Varying Adherence Rates For Paliperidone ER And Risperidone In Patients With Schizophrenia

Authors: DeVane CL, Passarell JA, Fiedler-Kelly J, Ludwig E, Martinez L, Canuso CM
Conference: U.S. Psychiatric and Mental Health Congress
Keywords: compliance, dopamine, dosage regimen, Phase 1, Phase 3, psychiatry, psychotherapeutic agents, steady state, target bounds, two-compartment model, virtual
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Medication adherence is important to successful management of • patients with schizophrenia and related psychotic disorders; patient nonadherence is documented in numerous studies (e.g., 30%-35%…

Simulation of Cilostazol Absorption and Pharmacokinetics

Simulation of Cilostazol Absorption and Pharmacokinetics

Authors: Lukacova V, Bolger MB, Crison JR, Woltosz WS
Conference: ISSX
Keywords: absorption, ACAT model, ADMET, Cilostazol, PBPK, Population Estimates for Age-Related (PEAR™) Physiology™
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

Cilostazol absorption and pharmacokinetics were simulated using GastroPlus™. The program’s Advanced Compartmental and Transit (ACAT) model described the absorption of the drug, while pharmacokinetics was…

Physiologically Based Model for Ketoconazole Disposition and Prediction of its Drug-Drug Interactions

Physiologically Based Model for Ketoconazole Disposition and Prediction of its Drug-Drug Interactions

Authors: Fraczkiewicz G, Lukacova V, Parrott N, Bolger MB, Crison JR, Woltosz WS, Lavé T
Conference: ISSX
Keywords: ADMET, Cp-Time, DDIs, drug-drug interactions (DDIs), ketoconazole, Kps, PBPK, PEAR, Population Estimates for Age-Related (PEAR™) Physiology™
Software: ADMET Predictor®, GastroPlus®
Division: PBPK

Ketoconazole is a potent inhibitor of the major drug-metabolizing enzyme, CYP3A4 and, as the result of that, is involved in many drug-drug interactions.  Pharmacokinetic (PK) information available for…

Forensic Pharmacometrics: Part 1 – Data Assembly

Forensic Pharmacometrics: Part 1 – Data Assembly

Authors: Grasela TH, Fiedler-Kelly J, Hitchcock D, Ludwig E, Passarell JA
Conference: ACoP
Keywords: analysis-ready dataset, data assembly, data checks, dataassembly, derived variables, dosing history, due diligence, EDA, exploratory data analysis, flag, forensic, NONMEM standards, PKPD methodology, quality assurance, requirements, steady state, verification
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Pharmacometric modeling and simulation (M&S) is moving from merely describing pharmacokinetic (PK) and pharmacodynamic (PD) phenomena to informing critical drug development and regulatory decision-making…

Population PK/PD Modeling of Efficacy and Safety of CB1R Inverse Agonist Taranabant in Obese Patients

Population PK/PD Modeling of Efficacy and Safety of CB1R Inverse Agonist Taranabant in Obese Patients

Authors: Li XS, Jin B, Fang L, Zhou HU, Passarell JA, Lu Q, Su J, Addy C, Erondu N, Suryawanshi S, Fiedler-Kelly J, Stone J
Conference: ACoP
Keywords: adverse events, AIC, Akaike's Information Criterion, biphasic logistic model, central nervous system agents, Emax, gastroenterology, indirect response model, linear logistic model, logistic regression model, longitudinal PK/weight loss model, neurology, PK/AE model, placebo, psychiatry, safety, steady state
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Taranabant is a cannabinoid-1 receptor (CB1R) inverse agonist, that was being developed by Merck and Co., Inc. as a potential treatment of obesity.

Exposure-response analyses of tigecycline tolerability in healthy subjects

Exposure-response analyses of tigecycline tolerability in healthy subjects

Authors: Passarell JA, Ludwig EA, Liolios K, Meagher AK, Grasela TH, Babinchak T, Ellis-Grosse EJ
Publication: Diagn Microbiol.Infect.Dis
Keywords: 80 and over, administration & dosage, adolescent, adult, adverse effects, aged, analogs & derivatives, anti-bacterial agents, chemically induced, female, humans, male, middle-aged, Minocycline, nausea, Probability, research, Tetracy, Tigecycline exposure
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Tigecycline exposure (area under the concentration-time curve [AUC((0-infinity))] and maximum serum concentration [C(max)]) and first occurrence of nausea and vomiting were evaluated in 136 healthy subjects after...

Practical Anticipation of Human Efficacious Doses and Pharmacokinetics Using In Vitro and Preclinical In Vivo Data

Practical Anticipation of Human Efficacious Doses and Pharmacokinetics Using In Vitro and Preclinical In Vivo Data

Authors: Heimbach T, Lakshminarayana SB, Hu W, He H
Publication: AAPS J
Keywords: dose-response, drug design, drug relationship, humans, in vitro techniques, pharmacokinetics
Software: GastroPlus®

Accurate predictions of human pharmacokinetic and pharmacodynamic (PK/PD) profiles are critical in early drug development, as safe, efficacious, and "developable" dosing...

The use of gastrointestinal intubation studies for controlled release development

The use of gastrointestinal intubation studies for controlled release development

Authors: Sutton SC
Publication: Br J Clin Pharmacol
Keywords: administration and dosage, animals, colon physiology, dogs, gastrointestinal, humans, intestinal absorption, permeability, solubility
Software: GastroPlus®

This review describes clinical results of gastrointestinal intubation studies of eight controlled release (CR) candidates under development during the 1990s and offer

Population pharmacokinetic analysis of linezolid in patients with infectious disease: application to lower body weight and elderly patients

Population pharmacokinetic analysis of linezolid in patients with infectious disease: application to lower body weight and elderly patients

Authors: Abe S, Chiba K, Cirincione B, Grasela TH, Ito K, Suwa T
Publication: J Clin Pharmacol
Keywords: 80 and over, Acetamides, adolescent, adult, Age Factors, aged, analysis, anti-bacterial agents, Asian Continental Ancestry Group, body weight, clinical trials, Communicable Diseases, drug therapy, Phase II as Topic, Phase III as Topic
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Linezolid (Zyvox), belonging to oxazolidinone antibiotics, is commonly used for the treatment of patients infected with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci.