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• Bioequivalence studies are used to compare early and late clinical trial formulations, formulations used in clinical trials and stability studies, if different, clinical trial formulations and to-be-marketed drug products, if different, product strength equivalence, as appropriate.
• A drug product that contains the same active drug substance in the same dosage form and is marketed by more than one pharmaceutical manufacturer is referred to as a multi-drug product.
• A single-source drug product is a product where the patent is not yet expired or has certain exclusivities so that only one manufacturer can make it.
• Approved products with therapeutic equivalence evaluations, also known as the Orange Book, identify drug products approved on the basis of safety and effectiveness by the FDA.
• A pharmaceutical equivalent is a drug product that contains the same active ingredients, salt, dosage form and strength, route of administration, and is therapeutically equivalent.
• A pharmaceutical alternative is a drug product that contains different active ingredients, salt, dosage form and strength, route of administration, and is therapeutically equivalent.
• Calculating the volume of an aqueous medium sufficient to dissolve the highest anticipated dose is known as Dissolution.
• CLINICAL OBSERVATIONS: LEAST accurate, LEAST sensitive, LEAST reproducible are the general approaches for determining in vivo Bioavailability.
• Bioavailability is classified based on the aqueous solubility of the drug and the permeability of the drug through the GI tract.
• The test formulation that demonstrates the MOST RAPID RATE OF DRUG BIOAVAILABILITY in vivo is generally the same as the one that dissolves the highest anticipated dose in vitro.
• PARAMETERS: total Area under the APE - time curve, peak pharmacodynamic effect time for peak pharmacodynamic effect.
• Classification of Bioavailability System (BCS) is: High Solubility and High Permeability (Class 1), Low Solubility and High Permeability (Class 2), High Solubility and Low Permeability (Class 3), Low Solubility and Low Permeability (Class 4).
• In vitro studies involve testing the test formulation that demonstrates the MOST RAPID RATE OF DRUG DISSOLUTION.
• Bioavailability studies are used to define the effect of changes in the physicochemical properties of the drug substance and the effect of the drug product (dosage form) on the pharmacokinetics of the drug.
• Bioequivalence studies are used to compare the bioavailability of the same drug (same salt or ester) from various drug products.
• Relative availability is the availability of the drug from a drug product as compared to a recognized standard.
• Absolute availability is the systemic availability of a drug after extravascular administration compared to IV dosing.
• dDu/dt is the rate of drug excretion and depends on the kinetic parameters k and Cp.
• t max is the time required to reach plasma drug concentration and is a measure of the rate of absorption.
• A timely urine sample must be collected for urinary drug excretion.
• The relative bioavailability of a drug can be greater than 100%.
• Urinary drug excretion is an indirect method, as the drug is not found in the urine unchanged.
• Plasma samples were obtained periodically up to 48 hours after the dose and assayed for drug concentration.
• Each volunteer received either a single oral tablet containing 200 mg of the drug, 5 mL of a pure aqueous solution containing 200 mg of the drug, or a single IV bolus injection containing 50 mg of the drug.
• AUC is the measurement of the extent of bioavailability, representing the total amount of drug that reaches the systemic circulation and is proportional to dose.
• C max is the maximum plasma concentration and provides that the drug is sufficiently systematically absorbed to provide therapeutic effect.
• Rate of absorption is the rate of elimination.
• Du is the cumulative amount of drug excreted in the urine.
• t is the time for the drug to be excreted and is a useful parameter in bioequivalence studies.
• The most direct and objective way to determine systemic drug bioavailability is through the measurement of time required to reach plasma drug concentration (t max), rate of absorption (rate of elimination), maximum plasma concentration (C max), and area under the curve (AUC).
• The bioavailability of a new investigational drug was studied in 12 volunteers.