Pharma Blog
Free Drug Hypothesis in Drug Discovery and Clinical Pharmacotherapy
Do we know why understanding the nuances associated with the free drug hypothesis is important for both drug discovery and clinical pharmacotherapy? Free drug hypothesis defines that (1) changes in drug action (pharmacodynamic or PD) is associated with changes in unbound drug concentration at target tissue (CuT), and (2) based ... Read More
Relation Between Renal clearance and Urine pH
Do we know why the renal clearance of some drugs (e.g. memantine) is sensitive to the change in urine pH? Memantine is a medication taken to slow the progression of moderate-to-severe Alzheimer’s disease. It is a basic (alkaline) and lipophilic (fat-liking) drug (pKa 10 and logP 3). Once memantine is ... Read More
Volume of Distribution (V)
Do we know that one of the most misunderstood pharmacokinetic (PK) parameters is volume of distribution (V)? This is especially exacerbated by the many terminologies of V. Let’s start with a simple yet important understanding that V is a proportionality factor that relates the amount of drug in the body ... Read More
Clinical Trial Terminologies | Part-2
KAPLAN-MEIER CURVE A graphical representation of survival probabilities over time in a clinical trial. HAZARD RATIO A measure comparing the risk of an event occurring in two groups over time. COX PROPORTIONAL HAZARDS MODEL A statistical method to explore the relationship between variables and time-to-event outcomes. DOSE-RANGING STUDY A study ... Read More
Clinical Trial Terminologies | Part-1
BLINDED ADJUDICATION A process where an independent committee reviews and classifies study outcomes without knowing which treatment group the participants belong to. SUBGROUP ANALYSIS An analysis conducted on specific subsets of participants (e.g., by age or gender) to explore differences in treatment effects. NON-INFERIORITY TRIAL A trial designed to demonstrate ... Read More
Differences Between RSABE and Traditional ABE Approaches
Scaling of Bioequivalence Limits RSABE (reference-scaled average bioequivalence): The limits are scaled based on the intra-subject variability of the reference drug. For drugs with higher variability, the acceptance criteria are relaxed, meaning the 90% confidence interval for the pharmacokinetic parameter ratios can be wider than the standard 80–125% used in ... Read More
Highly Variable Drugs and RSABE
Highly variable drugs (HVDs) are a category within pharmaceuticals that exhibit significant intra-subject variability in pharmacokinetic parameters such as peak concentration (Cmax) and the area under the concentration-time curve (AUC). Specifically, a drug is classified as highly variable when the intra-subject variability, represented by the coefficient of variation (CV), exceeds ... Read More
Special BE Considerations for Highly Variable and Narrow Therapeutic Index Drugs
High Variability Drugs (HVDs) and Narrow Therapeutic Index Drugs (NTIDs) represent unique challenges in bioequivalence (BE) studies due to their specific pharmacokinetic characteristics. HVDs typically exhibit high intra-subject variability in drug absorption and distribution, meaning that the pharmacokinetic response can vary significantly within the same individual across different doses. Conversely, ... Read More
How do We Ensure that Split Tablets Maintain Dose Accuracy and Stability?
For those who need flexible dosing, tablet splitting (for tablets with a functional score-line) can be helpful, but it’s essential to ensure each piece is consistent and effective. Here’s a quick look at the *key tests and acceptance criteria to assess splitting of scored immediate-release tablets. To ensure quality and ... Read More
How Glassware Could Be Sabotaging Your Dissolution Results?
We often assume that inconsistent or low drug release during dissolution testing to product performance issues or instability of the drug at a certain pH. But here’s the twist—sometimes the problem isn’t the drug or the formulation at all. The real culprit could be the glassware you’re using during the ... Read More
Food-Drug Interactions on Drug Safety & Efficacy
The FDA’s guidance Assessing the Effects of Food on Drugs in INDs and NDAs- Clinical Pharmacology Considerations, emphasizes the importance of Food-Effect (FE) studies in assessing how food influences the absorption, safety, and effectiveness of orally administered drugs during drug development. Here’s a breakdown of key takeaways: Why Food Effects ... Read More