Objective: To simulate and predict the absorption and pharmacokinetics(PK) of budesonide following intravenous(IV) and oral(PO) administrations.
Population Pharmacokinetic Evaluation of Eslicarbazepine Acetate for Adjunctive Therapy in Refractory Partial Onset Seizures
Eslicarbazepine acetate (ESL) is a once-daily antiepileptic drug (AED) that is converted to eslicarbazepine, the primary active metabolite of ESL, after oral administration. A population…
Tedizolid Population Pharmacokinetics, Exposure-Response, and Target Attainment
Tedizolid phosphate is a novel antibiotic prodrug rapidly converted by phosphatases to its active moiety tedizolid after administration. Tedizolid is 4-16 fold more potent in vitro than linezolid against…
Reduction in Interindividual Variability and Clinical Significance Ratio in Covariate Assessment
Covariate analysis has become a customary and expected part of population pharmacokinetic (PK) and pharmacokinetic/ pharmacodynamic (PK/PD) modeling.1 The covariate submodel describes, explains, and…
A Population PK Model for Cariprazine and the Metabolites
Cariprazine (CAR) is a potent dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors. Cariprazine was originally discovered by Gedeon Richter Plc. in Budapest, Hungary, and is…
Physiologically Based Pharmacokinetic (PBPK) Modeling of Amoxicillin in Neonates and Infants
An amoxicillin PBPK model was previously developed and validated in healthy adults as well as adults with altered renal function [1-2]. The purpose of this study was to explore the utility of the model in...
The Role of Paracellular and Carrier-Mediated Pathways in the Nonlinear Absorption of BCS Class III Substrates for Influx and Efflux Transporters
Mechanistic oral absorption simulation of nonlinear dose dependence for BCS Class III transporter substrates is an important objective in preclinical development of NCEs as well as in generic formulation…
Computational Exploration of the Role of a Prototypical Damage-Associated Molecular Pattern (DAMP) Molecule in Acetaminophen Hepatotoxicity
Drug-induced liver injury (DILI) is a major source of acute liver failure and is one of the leading causes of drug development failures. As such, there remains an important unmet need for earlier...
Pharmacokinetic Profile of an Ascending-Dose, Estrogen/Progestin Combination Oral Contraceptive
The estrogen component of oral contraceptives provides stability to the endometrium so that irregular shedding and unwanted breakthrough bleeding are minimized. An ascending-dose, extended-regimen…
The PK/PD Relationship of Ethinyl Estradiol and Unscheduled Bleeding or Spotting for an Ascending-dose, Estrogen/Progestin Combination Oral Contraceptive (OC)
The estrogen component of OCs provides stability to the endometrium so that irregular shedding and unwanted breakthrough bleeding are minimized. An ascending-dose, extended-regimen ethinyl estradiol…
Mechanistic Modeling Reveals the Most Important Unknowns in Bile Acid-Mediated DILI
BSEP inhibition and consequent bile acid (BA) buildup has been proposed to be an important mechanism in druginduced liver injury (DILI). There are many gaps in the knowledge of BA homeostasis and its…
DILIsym™, a Mechanistic Model of Drug-Induced Liver Injury, Supports the Interpretation of Elevated Liver Transaminase Levels in a Healthy Volunteer Pooled Safety Population for an Orphan Drug Designed for a Life-Threatening Situation
Compound A is in development for a life-threatening situation. The “Animal Rule” applies to efficacy, but not to safety assessment, which must be determined in humans. In a pooled safety population…
MembranePlus™: A Tool to Study in vitro/in vivo Transport and Lysosomal Trapping
To develop a mechanistic mathematical model for analysis of in vitro permeability assays that accounts for all mechanisms contributing to observed apparent permeability: passive paracellular and…
Design, Synthesis and Testing of Novel Antimalarial Drug Leads Using in silico Tools
The World Health Organization has estimated that over 200 million people suffered from malaria in 2010 and that over 600,000 people died from it that year [1]. Growing problems with resistance to existing anti…
PBPK Model Simulation of CYP3A4 and Transporter Mediated Drug-drug Interactions Involving Erythromycin
Erythromycin, a macrolide antibiotic, is cleared primarily by cytochrome P450-3A4 metabolism to the N-demethylated metabolite and C-formaldehyde. Its uptake into hepatocytes is mediated by organic…
Novel Antimalarial Drug Candidates Generated in silico by Analysis of Public HTS Data
Carry out a prospective experiment to demonstrate the ability of in silico drug design tools to design new lead drug candidates from phenotypic screening data.
Prediction of Amoxicillin Pharmacokinetics in Populations with Altered Renal Function
Purpose of the study was to predict amoxicillin pharmacokinetics in populations with altered renal function to further validate an absorption/PBPK model for amoxicillin.
Physiologically Based Pharmacokinetic (PBPK) Modeling of Amoxicillin Absorption and Pharmacokinetics
Purpose of the study was to develop a PBPK model for amoxicillin incorporating saturable transport processes affecting the drug’s absorption and distribution.
PBPK Modeling of Erythromycin Absorption and Disposition Mediated by Transporters in Humans
Erythromycin, a macrolide antibiotic, is cleared primarily by cytochrome P450-3A4 metabolism. Its uptake into enterocytes and hepatocytes is mediated by organic anion transporter (OAT) and organic anion…
In Silico Metabolite Prediction Using Artificial Neural Network Ensembles
Drug metabolism plays a crucial role in understanding bioavailability and drug-drug interactions, as well as in the design of prodrugs and in avoiding undesirable toxic metabolites.