Certara’s Best of Blogs 2015

A selection of short essays from our blog, written to empower our customers with biosimulation and regulatory writing solutions in order to help them solve the toughest drug development problems. Certara staff contributions range in topic from pharmacometrics to systems biology to the growing importance of regulatory writing.

Read More
Topics:

Modeling the Influence of Ethnicity on Drug Disposition

Zoe Barter

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 […]

Read More
Topics: PBPK Modeling & Simulation

Bottom-up Modeling and Simulation of Tacrolimus Clearance: Prospective Investigation of Blood Cell Distribution, Sex and CYP3A5 Expression as Covariates and Assessment of Study Power

The objectives were to investigate the ability of population-based in vitro-in vivo extrapolation (IVIVE) to reproduce the influence of haematocrit on the clearance of tacrolimus, observed previously, and to assess the power of clinical studies to detect the effects of covariates on the clearance of tacrolimus. A population-based pharmacokinetic simulator (Simcyp®) was used to simulate […]

Read More
Topics:

Differences in Cytochrome P450-mediated Pharmacokinetics Between Chinese and Caucasian Populations Predicted by Mechanistic Physiologically-based Pharmacokinetic Modeling

International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines emphasize the need for better understanding of the influence of ethnicity on drug response to minimize duplication of clinical studies, thereby expediting drug approval. We have developed a Chinese database for the prediction of differences in the population kinetics of drugs mainly metabolized […]

Read More
Topics:

Application of Permeability-limited Physiologically-based Pharmacokinetic Models: Part II—Prediction of P-glycoprotein Mediated Drug-drug Interactions with Digoxin

Digoxin is the recommended substrate for assessment of P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) in vivo. The overall aim of our study was to investigate the inhibitory potential of both verapamil and norverapamil on the P-gp-mediated efflux of digoxin in both gut and liver. Therefore, a physiologically-based pharmacokinetic (PBPK) model for verapamil and its primary metabolite […]

Read More
Topics:

Application of Permeability-limited Physiologically-based Pharmacokinetic Models: Part I—Digoxin Pharmacokinetic Incorporating P-glycoprotein-mediated Efflux

A prerequisite for the prediction of the magnitude of P-glycoprotein (P-gp)-mediated drug-drug interactions between digoxin and P-gp inhibitors (e.g. verapamil and its metabolite norverapamil) or P-gp inducers (e.g. rifampicin) is a predictive pharmacokinetic model for digoxin itself. Thus, relevant in vitro metabolic, transporter and inhibitory data incorporated into permeability-limited models, such as the “advanced dissolution, […]

Read More
Topics:

A Mechanistic Framework for In Vitro-In Vivo Extrapolation of Liver Membrane Transporters: Prediction of Drug-drug Interaction Between Rosuvastatin and Cyclosporine

The interplay between liver metabolizing enzymes and transporters is a complex process involving system-related parameters such as liver blood perfusion as well as drug attributes including protein and lipid binding, ionization, relative magnitude of passive and active permeation. Metabolism- and/or transporter-mediated drug–drug interactions (mDDIs and tDDIs) add to the complexity of this interplay. Thus, gaining meaningful insight into the impact of each element on […]

Read More
Topics:

Age Related Changes in Fractional Elimination Pathways for Drugs: Assessing the Impact of Variable Ontogeny on Metabolic Drug-drug Interactions

The magnitude of any metabolic drug-drug interactions (DDIs) depends on fractional importance of inhibited pathway which may not necessarily be the same in young children when compared to adults. The ontogeny pattern of cytochrome P450 (CYP) enzymes (CYPs 1A2, 2B6, 2C8, 2C9, 2C18/19, 2D6, 2E1, 3A4) and renal function were analyzed systematically. Bootstrap methodology was […]

Read More
Topics:
Learn More LinkedIn Twitter Facebook Email