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
Objectives: One of the hallmarks of pulmonary tuberculosis (TB) is the formation of granulomas, heterogeneous lesions composed of macrophage and neutrophil rich peripheral regions and a necrotic core, in the lungs of the infected host. Anti-TB drugs must penetrate these lesions to exert their effects. This work aimed to extend a permeability-limited lung model  […]Read More
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 […]Read More
What would you guess is the world’s most neglected disease? I bet that you wouldn’t pick tuberculosis (TB)— a disease that causes an estimated 9 million new cases and 1.3 million deaths annually. This infectious disease is caused by the bacterium Mycobacterium tuberculosis. TB usually attacks the lungs, but can attack any part of the body.
Patients infected with TB are typically treated with a standard six-month course of multiple antimicrobial drugs. It is quite difficult to get patients to adhere to this long course of treatment. Often, patients will fail to complete the entire drug course. This increases the likelihood of relapse and antibiotic resistance developing. Thus, there is an urgent need for shorter treatment regimens that minimize the risk of relapse. In this blog post, I’ll discuss how meta-regression modeling of relapse can inform TB clinical trial design.Read More
New regimens capable of shortening tuberculosis treatment without increasing the risk of recurrence are urgently needed. A 2013 meta-regression analysis, using data from trials published from 1973 to 1997 involving 7793 patients, identified 2-month sputum culture status and treatment duration as independent predictors of recurrence. The resulting model predicted that if a new 4-month regimen […]Read More
The purpose of this study was to evaluate the value of model-based, quantitative decision making during the development of gemcabene, a novel lipid-altering agent. The decisions were driven by a model of the likely clinical profile of gemcabene in comparison with its competitors, such as 3-hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), the cholesterol absorption inhibitor […]Read More