What Can We Learn from a Human Mass Balance Study?

Mass balance studies are also called “C-14 studies” or “Absorption, Metabolism, and Excretion (AME) studies”. It is important to understand what you are trying to learn from the experiment. The primary objectives of a mass balance study are generally: To determine the mass balance of drug-related material following dose administration To determine the ratio of … Continued

Accumulation: What It Means and How to Calculate It

A reader, Michael, asked me to discuss the concept of accumulation. This term is used frequently in both the nonclinical and clinical setting. Some people use the word with fear, while others explain it in complicated terms. Accumulation represents the relationship between the dosing interval and the rate of elimination for the drug. When the … Continued

Bioavailability

The term bioavailability is used very frequently in pharmacokinetic discussions. Often it is misused and complicated by those who don’t understand its meaning. Bioavailability simply means the fraction of administered drug that reached the systemic circulation (blood). It can range from 0% (no drug) to 100% (all of the administered drug). Absolute vs Relative The … Continued

Simulations Using a Drug-disease Modeling Framework and Phase 2 Data Predict Phase 3 Survival Outcome in First-line Non-small Cell Lung Cancer

Simulations were performed for carboplatin/paclitaxel (C/P) plus motesanib or bevacizumab vs. C/P as first-line treatment for advanced non small-cell lung cancer (NSCLC) using a published drug disease model. With 700 patients in each arm, simulated hazard ratios for motesanib (0.87; 95% confidence interval [CI], 0.71-1.1) and bevacizumab (0.89; 95% CI, 0.73-1.1) agreed with results from … Continued

Characterization of Exposure Versus Response of Edoxaban in Patients Undergoing Total Hip Replacement Surgery

Edoxaban is an oral direct factor Xa inhibitor approved for the prevention of venous thromboembolism (VTE) in Japan. The objectives of this analysis were to characterise the population pharmacokinetics (PK) of edoxaban and the relationships between edoxaban exposure and clinical outcomes in a phase IIb study of surgical patients following total hip replacement (THR). A … Continued

Trends in Oral Drug Bioavailability Following Bariatric Surgery: Examining the Variable Extent of Impact on Exposure of Different Drug Classes

Changes to oral drug bioavailability have been observed post bariatric surgery. However, the magnitude and the direction of changes have not been assessed systematically to provide insights into the parameters governing the observed trends. Understanding these can help with dose adjustments. Analysis of drug characteristics based on a biopharmaceutical classification system is not adequate to … Continued