GPAT Biopharmaceutics and Pharmacokinetics Syllabus

What is the most common Phase II conjugation reaction and the enzyme involved?

Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) using UDP-glucuronic acid as the cofactor.

What is the first-pass (presystemic) metabolism effect?

The metabolism of an orally administered drug in the gut wall and liver before it reaches the systemic circulation, reducing its bioavailability.

Define a prodrug.

An inactive (or less active) compound that is converted by metabolism in the body into the active drug, e.g., enalapril to enalaprilat.

What is the difference between an enzyme inducer and an enzyme inhibitor?

An inducer (e.g., rifampicin, phenobarbital) increases CYP enzyme synthesis, increasing metabolism and decreasing drug levels; an inhibitor (e.g., ketoconazole, erythromycin) decreases enzyme activity, increasing drug levels and toxicity risk.

Define drug excretion and name the major route.

The irreversible removal of drug and its metabolites from the body. The kidney is the major organ, eliminating drugs via urine.

Name the three processes of renal drug excretion.

Glomerular filtration, active tubular secretion, and passive tubular reabsorption.

How does urine pH affect renal excretion of weak acids and bases?

Alkalinizing urine increases ionization and excretion of weak acids (e.g., aspirin); acidifying urine increases ionization and excretion of weak bases (e.g., amphetamine), because ionized drug is not reabsorbed.

Define renal clearance and give its formula.

The volume of plasma cleared of drug by the kidneys per unit time. Renal clearance = (Urine concentration × Urine flow rate) / Plasma concentration = (U·V)/P.

What is enterohepatic recirculation?

The cycle in which a drug excreted in bile into the intestine is reabsorbed back into the circulation, prolonging its half-life and duration of action.

Define total body clearance (systemic clearance).

The sum of all clearances (hepatic, renal, and other). ClT = Cl_renal + Cl_hepatic + others; ClT = (k × Vd) = Dose/AUC for IV administration.

Define bioavailability (F).

The rate and extent to which the active drug is absorbed and becomes available at the site of action (systemic circulation). It is expressed as a fraction or percentage of the administered dose reaching circulation unchanged.

What is the bioavailability of an intravenous drug, and why?

100% (F = 1), because the drug is introduced directly into the systemic circulation, bypassing absorption and first-pass metabolism.

Differentiate absolute and relative bioavailability with their formulas.

Absolute BA = (AUC_oral × Dose_IV)/(AUC_IV × Dose_oral), comparing extravascular to IV. Relative BA = (AUC_test × Dose_std)/(AUC_std × Dose_test), comparing two non-IV formulations.

What pharmacokinetic parameter measures the EXTENT of bioavailability, and which measures the RATE?

Extent of absorption is measured by AUC (area under the curve); rate of absorption is reflected by Cmax (peak concentration) and Tmax (time to peak).

What does AUC (area under the plasma concentration-time curve) represent?

The total systemic exposure to the drug — the total amount of unchanged drug that reaches the systemic circulation; it is proportional to the extent of absorption.

List major factors affecting bioavailability.

Physicochemical factors (solubility, particle size, polymorphism, salt form), pharmaceutical factors (dosage form, excipients, manufacturing), first-pass metabolism, GI factors (pH, motility, food), and patient/disease factors.

How does particle size affect bioavailability of poorly soluble drugs?

Reducing particle size increases surface area, enhancing dissolution rate and thus bioavailability (e.g., micronization of griseofulvin).

How can polymorphism affect bioavailability?

Different crystalline forms (polymorphs) have different solubilities and dissolution rates; the metastable (amorphous) form usually dissolves faster, giving higher bioavailability than the stable crystalline form.

How does food generally affect drug bioavailability?

Food can delay gastric emptying and slow absorption rate; it may decrease absorption of some drugs (e.g., tetracyclines chelate with food cations) or increase absorption of lipophilic drugs (e.g., griseofulvin).

Define bioequivalence.

Two pharmaceutically equivalent products are bioequivalent if their rate and extent of absorption (bioavailability) do not differ significantly when administered at the same molar dose under similar conditions.

What is the regulatory acceptance criterion (confidence interval) for bioequivalence?

The 90% confidence interval of the ratio (test/reference) of the geometric means for AUC and Cmax must fall within 80.00%–125.00%.

What study design is most commonly used for bioequivalence studies?

A randomized, two-period, two-sequence, single-dose crossover design in healthy volunteers, with an adequate washout period between treatments.

Differentiate pharmaceutical equivalents and pharmaceutical alternatives.

Pharmaceutical equivalents contain the same active ingredient, strength, dosage form, and route. Pharmaceutical alternatives contain the same active moiety but may differ in salt/ester form, strength, or dosage form.

What is a therapeutic equivalent?

A drug product that is pharmaceutically equivalent AND bioequivalent, so it can be expected to have the same clinical effect and safety profile as the reference product.

Define mean, median, and mode in descriptive statistics.

Mean = arithmetic average of all values; Median = middle value when data are ordered; Mode = the most frequently occurring value.

Differentiate standard deviation and standard error of the mean (SEM).

Standard deviation (SD) measures the dispersion of individual data points around the mean. SEM = SD/√n, measures the precision of the sample mean as an estimate of the population mean; SEM decreases as sample size increases.

What is the difference between descriptive and inferential statistics?

Descriptive statistics summarize and describe data (mean, SD, frequency). Inferential statistics use sample data to make generalizations or draw conclusions about a population (hypothesis testing, confidence intervals).

Define null hypothesis (H0) and alternative hypothesis (H1).

H0 states there is no significant difference/effect (status quo); H1 states there is a significant difference/effect. Statistical testing aims to reject or fail to reject H0.

Distinguish Type I and Type II errors.

Type I error (α): rejecting a true null hypothesis (false positive). Type II error (β): failing to reject a false null hypothesis (false negative). Power = 1 − β.

When is a Student's t-test versus ANOVA used in biostatistics?

A t-test compares the means of two groups; ANOVA (analysis of variance) compares the means of three or more groups. A p-value < 0.05 is conventionally considered statistically significant.