Pharma Blog
Key Considerations for Generic Formulation Development
Generic formulation development is a complex process designed to create bioequivalent, cost-effective alternatives to innovator products while meeting regulatory standards. Below are the critical aspects to consider: Regulatory Compliance Ensure adherence to market-specific regulatory guidelines, such as those of USFDA, EMA, or MHRA, to obtain approval for generic products. Bioequivalence ... Read More
Citrus Food with Substrate of Pgp and CYP3A4
Do we know that jabara is a Japanese citrus that is similar to yuzu and is consumed as an anti-allergic functional food in Japan and worldwide? We have previously discussed how grapefruit juice interacts with medications (drugs). A question arises: does jabara also interact with drugs? Guess what? It has ... Read More
Concepts of Elimination Rate and Clearance of Drugs
Have we come across a presenter who commented that the ‘clearance rate of a drug is high or low’? A question arises: Is clearance an elimination rate of a given drug? Some of us remain unclear regarding the concepts of elimination rate and clearance of drugs. Elimination rate is the ... Read More
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