Bioavailability

What is bioavailability?

It’s the rate and extent to which the active drug ingredient is absorbed and becomes available at the site of action

Define bioequivalence.

Bioequivalence refers to two drug products showing comparable bioavailability under similar conditions​

What factors influence the bioavailability of a drug?

Factors include formulation, gastric emptying rate, and the drug's physicochemical properties

What are the three steps in the absorption of orally administered drugs?

Disintegration, dissolution, and transfer across the gastrointestinal membrane

What does the term “pharmaceutical equivalent” mean?

Products with the same active ingredients, dosage form, and strength, differing only in non-active characteristics​

What are therapeutic equivalents?

Pharmaceutical equivalents that provide the same clinical effect and safety profile

What is absolute bioavailability?

The fraction of a dose that reaches systemic circulation when compared to intravenous administration

What is relative bioavailability?

It compares the bioavailability of a drug product to another form of the same drug at the same dose

How does food affect drug absorption?

Food can increase or decrease drug absorption, depending on the drug’s properties

How is the area under the curve (AUC) used in bioavailability studies?

AUC measures the total drug exposure over time, helping compare different drug products

Why is a crossover study design preferred in bioavailability testing?

It minimizes inter-subject variability by using the same subjects for each product

What is the purpose of the washout period in crossover studies?

To ensure complete drug elimination between different test periods​

What is the FDA’s role in bioequivalence testing?

The FDA imposes bioequivalence requirements for generic drug approval​

What are pharmaceutical alternatives?

Drug products with the same therapeutic ingredient but different forms or strengths

What is the significance of the pKa of a drug?

pKa affects a drug’s ionization, impacting its solubility and absorption

Why are dissolution studies important in bioavailability?

They determine how quickly the drug dissolves, influencing absorption rate

How does particle size affect drug absorption?

Smaller particles dissolve faster, potentially increasing bioavailability

What is the Biopharmaceutics Classification System (BCS)?

It categorizes drugs based on solubility and permeability to predict bioavailability

What are the four BCS classes?

Class 1: high solubility, high permeability; Class 2: low solubility, high permeability; Class 3: high solubility, low permeability; Class 4: low solubility, low permeability​

What types of drugs are eligible for biowaivers in BCS?

Class 1 drugs, unless they have a narrow therapeutic range​

What is the impact of gastric emptying on drug absorption?

Delayed gastric emptying can slow drug absorption and onset time​

What is a bioavailability study?

It evaluates the absorption and availability of a drug in the body​

How does drug stability affect bioavailability?

Instability, especially in the gastrointestinal environment, can decrease bioavailability

What role does the blood level study play in bioavailability testing?

It monitors drug concentration in blood over time to assess absorption

Why is IV administration used as a reference in bioavailability studies?

IV administration ensures complete drug availability in systemic circulation

How does the AUC relate to bioavailability?

A higher AUC indicates greater bioavailability of a drug​

What is the impact of different salt forms on drug absorption?

Salt forms can alter drug solubility and, subsequently, absorption rate

Define therapeutic window.

The range of drug concentration that provides therapeutic effect without toxicity​

What is an excipient?

An inactive substance used to formulate a drug product

Why are clinical bioavailability studies complex and costly?

They require large populations, precise measurement, and controlled conditions

Why is AUC used to compare oral and IV drug products?

It helps calculate the fraction of the drug absorbed through the oral route​

What are the characteristics of an ideal test subject for bioavailability studies?

Healthy, normal weight, and aged 18-35

What is a generic drug?

A drug product that is bioequivalent to a branded product, offering the same therapeutic effect

How does age affect drug absorption?

Elderly and infants may experience altered absorption due to physiological differences

What is a bioequivalence study?

A test comparing the bioavailability of two dosage forms of the same drug​

Why must test and reference drugs be administered in a fasting state?

To reduce variability in absorption caused by food

What does tmax represent?

The time to reach the maximum concentration of drug in the blood​

Why is informed consent essential in clinical studies?

Participants must understand the study risks and benefits

What is urinary excretion data used for in bioavailability testing

To estimate the drug amount absorbed by measuring drug in urine​

What is the role of polymorphism in drug bioavailability?

Different crystal forms can have varying solubilities, affecting bioavailability​

How does lipophilicity influence drug absorption?

Higher lipophilicity may improve membrane permeability​

Why are cross-over designs commonly used in bioequivalence studies?

They help control individual variations by comparing results within each subject​

Why do drugs with narrow therapeutic ranges need careful bioequivalence testing?

Small differences in bioavailability can lead to therapeutic failure or toxicity​

What is the difference between absolute and relative bioavailability?

Absolute compares to IV administration; relative compares two oral products​

How does solubility impact drug absorption?

Poorly soluble drugs dissolve slower, reducing absorption​

What are the three major pharmacokinetic parameters in bioavailability studies?

Cmax, tmax, and AUC

What are the advantages of using blood level studies?

They provide a direct relationship between blood concentration and absorption

Why might multiple assays be needed in bioavailability studies?

To detect drug concentration changes over time

What is a biowaiver?

Exemption from in vivo bioavailability studies based on BCS classification​

Why should smokers be avoided in bioavailability studies?

Smoking can alter enzyme activity, affecting drug kinetics​

What is the impact of drug formulation on bioavailability?

Different formulations can alter the rate and extent of absorption​

Why is particle size reduction beneficial for poorly soluble drugs?

It increases surface area, enhancing dissolution

What factors affect the gastric emptying rate?

Drug formulation, food, and patient’s physiological conditions

What is a placebo?

A dosage form without an active ingredient, used as a control in studies

What is the purpose of comparing bioequivalence in generic drugs?

To ensure they provide the same therapeutic efficacy as branded drugs​

How does hydration affect drug bioavailability?

Hydrates may dissolve differently, impacting absorption​

What does F = 1 indicate in bioavailability?

Complete absorption of a drug

Why is pH important in drug absorption?

It affects ionization, influencing membrane passage​

Why are fasted conditions preferred in bioequivalence studies?

It reduces food effects on absorption​

What is meant by ‘drug product’?

A finished dosage form containing the drug and other inactive ingredients

How does disintegration time affect bioavailability?

Faster disintegration can improve the rate of absorption

What is the purpose of statistical analysis in bioequivalence?

To determine if differences between products are significant

What is kel in pharmacokinetics?

The elimination rate constant of a drug

Why is AUC crucial in drug comparisons?

It reflects the total exposure of the body to the drug

How does compression force in manufacturing affect tablets?

It can alter disintegration and dissolution rates, impacting bioavailability

What is a cross-over study?

A design where each subject receives multiple treatments in random order

What happens to drugs that are acid-labile in the stomach?

They may decompose, reducing bioavailability

How does the FDA define a bioequivalent drug product?

Pharmaceutical equivalents showing comparable bioavailability

Why is randomization important in study design?

It reduces bias and ensures reliable results

What is a dosage form?

The form in which a drug is produced, such as tablet or capsule

What is the difference between polymorph and amorph?

Polymorphs have structured forms, while amorphs lack a defined structure

Why is the Orange Book relevant for pharmacists?

It lists bioequivalent drug products for therapeutic substitution

What factors influence dissolution rate?

Particle size, solubility, and formulation

Why must blood samples be frequently collected in bioavailability studies?

To accurately determine pharmacokinetic parameters

What effect does ionization have on drug absorption?