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Relationship Between AUC and Volume of Distribution

A few days ago on the pharmacokinetics listserve PharmPK, the following question appeared: I’m having trouble wrapping my head around this question from an online pharmacology quiz.  The question is “The larger the volume of distribution, the smaller the AUC of a given drug.”  The answer is given as “False.” As I look at the … Continued

Where Did the 80-125% Bioequivalence Criteria Come From?

Most people involved in clinical pharmacokinetics are familiar with the 80-125% criterion. This criterion is used to compare two treatments with the purpose of evaluating if the treatments are bioequivalent. But, where did this come from? Why 80-125%? Why not 90-110%? or why not 80-120%? Before we explain where 80-125% came from, let me explain … Continued

Deciding on Which Drug-drug Interactions to Evaluate in the Clinic

Drug-drug interactions are a critical research area in pharmaceutical drug development. One of the most tragic examples of drug-drug interactions was the antihistamine terfenadine. Terfenadine (also known as Seldane) was a common antihistamine intended to block the effects of an allergic rhinitis. Upon administration terfenadine is metabolized to fexofenadine by the cytochrome P450 3A4 isoform. … Continued

Generics and Bioequivalence

As the debate about health care in the United States continues forward, the term “generic drugs” has become rather commonplace. What are generic drugs? Are they safe to use? Why do we have them? And what is bioequivalence? All of these are common questions that I hope to answer with my post today. What are … Continued

What are Compartmental Models?

Almost everyone familiar with pharmaceuticals has heard a conversation like this before: Scientist 1: “What are the pharmacokinetics of Drug X?” Scientist 2: “Drug X follows a 1-compartment model in rats, but in monkeys it tends to have a distribution phase and seems to follow 2-compartment kinetics.” Scientist 1: Thinks to himself/herself …’What does a … Continued

What are Drug-drug Interactions Anyway?

A current buzz phrase in pharmaceutical research right now is “drug-drug interaction” or simply “drug interaction”. The definition of a drug-drug interaction has fluctuated over the last few years, not because of changes in research, but because of misconceptions in the research community. The US Food and Drug Administration (FDA) has published a draft guidance … Continued

Trial Designs—Non-inferiority vs. Superiority vs. Equivalence

The primary purpose of a clinical trial is to address a scientific hypothesis. To address a hypothesis, different statistical methods are used depending on the type of question to be answered. Most often the hypothesis is related to the effect of one treatment as compared to another. For example, one trial could compare the effectiveness … Continued

Assessment of Algorithms for Predicting Drug-drug Interactions Via Inhibition Mechanisms: Comparison of Dynamic and Static Models

The prediction of drug-drug interactions (DDIs) from in vitro data usually utilizes an average dosing interval estimate of inhibitor concentration in an equation-based static model. Simcyp®, a population-based ADME simulator, is becoming widely used for the prediction of DDIs and has the ability to incorporate the time-course of inhibitor concentration and hence generate a temporal … Continued

3D-QSAR Studies on Caspase-mediated Apoptosis Activity of Phenolic Analogs

Phenols and its analogues are known to induce caspase-mediated apoptosis activity and cytotoxicity on various cancer cell lines. In the current work, two types of molecular field analysis techniques were used to perform the three dimension quantitative structure activity relationship (3D-QSAR) modeling between structural characters and anticancer activity of two sets of phenolic compounds, which … Continued

The Role of the Breast Cancer Resistance Protein (ABCG2) in the Distribution of Sorafenib to the Brain

ATP-binding cassette transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) have been shown to work in concert to restrict brain penetration of several tyrosine kinase inhibitors. It has been reported that P-gp is dominant in limiting transport of many dual P-gp/BCRP substrates across the blood-brain barrier (BBB). This study investigated the influence of P-gp … Continued

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