Obeticholic Acid – From PK Model to Drug Label

Watch this webinar with Jeffrey Edwards to learn how he used physiologic pharmacokinetic modeling to understand the relationship between systemic and hepatic exposure of OCA in patients with and without hepatic impairment. By watching this webinar, you will learn how pharmacokinetic modeling can support optimal dosing for patients with organ impairment and facilitate regulatory approval.

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Understanding the Relationship between Systemic and Hepatic Exposure of Obeticholic Acid for the Treatment of Liver Disease in Patients with Cirrhosis

Obeticholic acid (OCA) is a selective and potent farnesoid X receptor (FXR) agonist in development for several chronic liver diseases. OCA is a semi-synthetic analogue of chenodeoxycholic acid (CDCA) with similar pharmacokinetic (PK) properties. There was a significant increase in systemic exposure of OCA in patients with hepatic impairment. A proportionally similar increase in systemic […]

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Highlights of the Quebec “Drug Discovery to Development” Symposium

Mark Reimer

In today’s drug development climate, we’re encouraged to “think global, act local.” I have had the privilege of supporting the development of important new therapies for clients around the globe. But sometimes, it is helpful to take a step back and look at the exciting science going on in your own backyard. With that spirit […]

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Topics: PK/PD Modeling & Simulation

Pharmacokinetic Profile of Defibrotide in Patients with Renal Impairment

Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable, potentially life-threatening complication of hematopoietic stem cell transplant conditioning. Severe VOD/SOS, generally associated with multiorgan dysfunction (pulmonary or renal dysfunction), may be associated with >80% mortality. Defibrotide, recently approved in the US, has demonstrated efficacy treating hepatic VOD/SOS with multiorgan dysfunction. Because renal […]

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The Rise of Model-informed Drug Development in China

Christine Yuying Gao

China’s pharmaceutical market is poised for growth. By 2020, it is expected to grow to approximately $120 billion. Today, China’s 1.36 billion people represent 20 percent of the world’s population. Yet, they comprise only 1.5 percent of the global drug market. From a demographic perspective, nine percent of the Chinese population today is over 65 […]

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Topics: PBPK Modeling & Simulation, PK/PD Modeling & Simulation

How Biosimulation Can Bring New Immuno-oncology Treatments to Patients

Rik de Greef

Immuno-oncology, which harnesses the patient’s own immune system to fight cancer, is one of the hottest areas in drug development today. In recent years, the FDA has granted breakthrough therapy designations to multiple immuno-oncology drugs for a variety of oncology indications including advanced non-small cell lung cancer and melanoma. Over the last two decades, PK/PD […]

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Topics: PK/PD Modeling & Simulation

Pharmacokinetics of Tramadol and O-Desmethyltramadol Enantiomers Following Administration of Extended-release Tablets to Elderly and Young Subjects

Tramadol is frequently used in geriatric patients; however, pharmacokinetic (PK) publications on tramadol and O-desmethyltramadol (ODM) in elderly patients are rare. Our objective was to characterize the PK of tramadol and ODM, including absorption processes and covariates for tramadol, in elderly and young subjects after single-dose administration of 200-mg extended-release tablets. We conducted a PK […]

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Development of a Multicompartment Permeability-limited Lung PBPK Model and Its Application in Predicting Pulmonary Pharmacokinetics of Antituberculosis Drugs

Achieving sufficient concentrations of antituberculosis (TB) drugs in pulmonary tissue at the optimum time is still a challenge in developing therapeutic regimens for TB. A physiologically based pharmacokinetic model incorporating a multi-compartment permeability-limited lung model was developed and used to simulate plasma and pulmonary concentrations of seven drugs. Passive permeability of drugs within the lung was predicted using an in vitro-in vivo extrapolation approach. Simulated epithelial lining fluid (ELF):plasma concentration ratios showed reasonable […]

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The Anatomy of a Great Biosimulation Project

Nastya Kassir

In therapeutic areas with tough competition, it is challenging to establish a complete, confident understanding of a drug’s safety and efficacy profile. Any misunderstanding of a drug’s characteristics can derail the entire development program. Biosimulation, also known as model based drug development, uses a number of techniques, such as population PK modeling, model-based meta-analysis, and […]

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Topics: PK/PD Modeling & Simulation

Population Pharmacokinetic Modeling of Motesanib and Its Active Metabolite, M4, in Cancer Patients

Motesanib is a small molecule and potent multikinase inhibitor with antiangiogenic and antitumor activity. Population pharmacokinetic (POPPK) modeling of motesanib and M4, an active metabolite, was performed to assess sources of variability in cancer patients. The analysis included data collected from 451 patients from 8 clinical trials with oral doses of motesanib ranging from 25 […]

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A Change of Heart at the Cardiac Safety Research Consortium

Christine Garnett

The ICH E14 guidance recommends that all new drugs with systemic bioavailability are assessed for the ability to delay cardiac repolarization as measured by the QT/QTc interval on the surface ECG. For most drugs, this evaluation is performed in the Thorough QT/QTc (TQT) study. Could using model-based approaches during routine early studies influence the current […]

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Topics: PK/PD Modeling & Simulation
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