We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity.
Modeling and simulation of the effect of proton pump inhibitors on magnesium homeostasis: part I. oral absorption of magnesium
Prolonged use of proton pump inhibitors has reportedly caused rare clinically symptomatic hypomagnesemia.
Application of ED-optimality to screening experiments for analgesic compounds in an experimental model of neuropathic pain
In spite of the evidence regarding high variability in the response to evoked pain, little attention has been paid to its impact on the screening of drugs for inflammatory and neuropathic pain.
Optimised protocol design for the screening of analgesic compounds in neuropathic pain
We have previously shown how screening experiments for neuropathic pain can be optimised taking into account parameter and model uncertainty.
Toxicological considerations of acetylcholinesterase reactivators
The more or less systematic studies on the specific activity of oximes as reactivators of acetylcholinesterase (AChE) inhibited by organophosphorus (OP) compounds...
Integrated Pharmacokinetic-Driven Approach to Screen Candidate Anticancer Drugs for Brain Tumor Chemotherapy
The goal of the study was to develop an effective screening strategy to select new agents for brain tumor chemotherapy from a series of low molecular weight anticancer...
Dynamic Change of Heme Environment in Soluble Guanylate Cyclase and Complexation of NO-Independent Drug Agents with H-NOX Domain
Soluble guanylate cyclase is a heterodimer receptor that functions in several signal transduction pathways. Conversion of guanosine 5'-triphosphate to...
Nilotinib preclinical pharmacokinetics and practical application toward clinical projections of oral absorption and systemic availability
Nilotinib is a highly potent and selective bcr-abl tyrosine kinase inhibitor used for the treatment of patients who are in the chronic and accelerated phases of...
Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling
To develop and evaluate a whole-body physiologically based pharmacokinetic (WB-PBPK) model of bisoprolol and to simulate its exposure and disposition...
Pharmacokinetics and Pharmacodynamics of Phase II Drug Metabolizing / Antioxidant Enzymes Gene Response by Anti-cancer Agent Sulforaphane in Rat Lymphocytes
This study assesses the pharmacokinetics (PK) and pharmacodynamics (PD) of Nrf2-mediated increased expression of phase II drug metabolizing enzymes (DME)...
In vitro to in vivo extrapolation and species response comparisons for drug-induced liver injury (DILI) using DILIsym™: a mechanistic, mathematical model of DILI.
Drug-induced liver injury (DILI) is not only a major concern for all patients requiring drug therapy, but also for the pharmaceutical industry.
Effects of parabens on adipocyte differentiation
Parabens are a group of alkyl esters of p-hydroxybenzoic acid that include methylparaben, ethylparaben, propylparaben, butylparaben, and benzylparaben.
The Use of Modeling Tools to Drive Efficient Oral Product Design
Modeling and simulation of drug dissolution and oral absorption has been increasingly used over the last decade to understand drug behavior in vivo based on the physicochemical properties of Active...
Preclinical Assessment of the Absorption and Disposition of the Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Inhibitor GDC-0980 and Prediction of Its Pharmacokinetics and Efficacy in Human
The objectives of these studies were to characterize the absorption and disposition of GDC-0980 and assess its efficacy in an MCF7-neo/HER2 human breast cancer xenograft model in immunocompromised mice.
Application of PBPK modeling to predict human intestinal metabolism of CYP3A substrates – An evaluation and case study using GastroPlus™
First pass metabolism in the intestinal mucosa is a determinant of oral bioavailability of CYP3A substrates and so the prediction of intestinal availability (Fg) of potential drug candidates is important.
Comparison of in vitro–in vivo release of Risperdal® Consta® microspheres
The objective was to investigate the relationship between in vitro and in vivo release of commercial Risperdal® Consta® microspheres.
Regioselective oxidation of phospho-NSAIDs by human cytochrome P450 and flavin monooxygenase isoforms: implications for their pharmacokinetic properties and safety
Phospho-ibuprofen (MDC-917) and phospho-sulindac (OXT-328) are highly effective in cancer and arthritis treatment in preclinical models. Here, we investigated their metabolism by...
Predicting feasibility and characterizing performance of extended-release formulations using physiologically based pharmacokinetic modeling
This review presents nine case studies where physiologically based pharmacokinetic modeling has been used in the design and development of extended-release formulations.
Enhanced evaluation of selective androgen receptor modulators in vivo
Selective androgen receptor modulators (SARMs) are a class of drugs that control the activity of the androgen receptor (AR), which mediates the response to androgens, in a...
An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury
N-acetylcysteine (NAC) is the treatment of choice for acetaminophen poisoning; standard 72-h oral or 21-h intravenous protocols are most frequently used.