Modeling the Influence of Ethnicity on Drug Disposition

Ever noticed how people from different ethnic backgrounds respond differently to drugs? For example, you may enjoy having a few drinks with friends on the weekend.  When your friends with Eastern Asian heritage drink alcohol, it’s not uncommon for their faces to turn red. This happens because many East Asians possess an enzyme deficiency for … Continued

Assessing the Impact of Liver or Kidney Disease on Pharmacokinetics

Impaired hepatic or renal function can have a major impact on pharmacokinetics. There is a high risk of adverse events in patients with these conditions. Major pharmaceutical companies and drug regulatory agencies use physiologically-based pharmacokinetic (PBPK) modeling in virtual populations to investigate the impact of hepatic or renal impairment on drug exposure as a supplement to … Continued

Standardizing TK and Other NCA Analysis Reports with Phoenix Connect

Phoenix Connect’s Reporter allows users to construct a report within the Phoenix workflow and have the graphs, tables and listings generated by WinNonlin as well as third-party tools like SAS, NONMEM and R inserted directly into their Word report template. This demonstration focused on a bioavailability protocol.

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 … Continued

Using Modeling and Simulation to Optimize Dosing of an Anti-infective for Children

Pediatric drug development can, in many ways, be described as a “Catch 22.” It is extremely challenging (both logistically and ethically) to enroll children in clinical trials, yet without a proper and approved clinical process, physicians are left with inaccurate dosing and therapeutic approaches for children. Modeling and simulation methods, including population PK modeling, are … Continued

Postcards from the Road: Phoenix Fall Tour

We’ve just returned from the third leg of our now annual Phoenix roadshow. In this leg, I helped deliver workshops in Beijing, Osaka and Tokyo. In total, our product development team has visited eight cities in the US, Europe and Asia.  We gave both technical and scientific PK/PD modeling presentations to more than 250 clients. … Continued

9 Frequently Misunderstood Concepts in PK/PD Modeling

In teaching pharmacometrics, I’ve noticed that scientists have difficulty with certain PK/PD modeling concepts. Maybe you’ve read about some of these terms in journal articles, but didn’t know what they meant? Or you’ve heard these terms bandied about by colleagues, but felt too shy to ask them what they meant? I’ll clarify some important concepts … Continued

FDA Equips its Pharmacometrics Teams with Certara’s Phoenix Software

Partnership provides pharmacometric biosimulation solutions for multiple FDA centers PRINCETON, NJ – Nov. 2, 2015 – Certara®, the global biosimulation technology-enabled drug development company, today announced that the United States Food and Drug Administration (FDA) has outfitted its pharmacometrics teams with Certara’s Phoenix® software. Phoenix is the industry’s premier software platform for managing, analyzing and reporting … Continued

Interplay of Metabolism and Transport in Determining Oral Drug Absorption and Gut Wall Metabolism: A Simulation Assessment Using the “Advanced Dissolution, Absorption, Metabolism (ADAM)” Model

Bioavailability of orally administered drugs can be influenced by a number of factors including release from the formulation, dissolution, stability in the gastrointestinal (GI) environment, permeability through the gut wall and first-pass gut wall and hepatic metabolism. Although there are various enzymes in the gut wall which may contribute to gut first pass metabolism, Cytochrome … Continued