Individualization of drug dosage regimen: sources of variability MCQs With Answer

Introduction: Individualization of drug dosage regimens is central to safe and effective pharmacotherapy. This set of MCQs focuses on the sources of variability that influence individual responses to drugs — genetic factors, age, organ function, body composition, drug interactions, disease states, adherence, and environmental factors. Designed for M.Pharm students, the questions balance mechanistic understanding (pharmacokinetic and pharmacodynamic determinants) with clinical applications such as therapeutic drug monitoring, dose adjustment strategies, pharmacogenetics, and population pharmacokinetics. Working through these MCQs will strengthen your ability to identify causes of interindividual and intraindividual variability and apply that knowledge to tailor dosing for improved outcomes.

Q1. What combination best represents the major sources of interindividual variability that must be considered when individualizing a drug dosage regimen?

• Manufacturing variability and storage conditions
• Genetic polymorphisms, organ function, drug interactions and adherence
• Color of formulation and pill size
• Prescribing physician’s experience only

Correct Answer: Genetic polymorphisms, organ function, drug interactions and adherence

Q2. How do CYP450 genetic polymorphisms commonly influence drug dosing decisions?

• They only affect drug absorption, not metabolism
• They alter metabolic clearance leading to predictable changes in drug exposure
• They invariably increase clearance for all drugs
• They only affect biologic agents, not small molecules

Correct Answer: They alter metabolic clearance leading to predictable changes in drug exposure

Q3. Renal impairment most directly affects which pharmacokinetic parameter for primarily renally excreted hydrophilic drugs?

• Volume of distribution due to fat accumulation
• Renal clearance leading to prolonged elimination half-life
• Oral bioavailability by increasing first-pass metabolism
• Protein binding increasing plasma albumin levels

Correct Answer: Renal clearance leading to prolonged elimination half-life

Q4. Hepatic impairment has the greatest impact on drugs with which characteristic?

• High renal excretion and low hepatic extraction ratio
• High hepatic extraction ratio and significant first-pass metabolism
• Extremely low protein binding and no metabolism
• Exclusive lung elimination

Correct Answer: High hepatic extraction ratio and significant first-pass metabolism

Q5. How does hypoalbuminemia alter pharmacokinetics of highly protein-bound acidic drugs?

• Decreases free (unbound) drug fraction and reduces pharmacologic effect
• Increases free drug fraction, potentially increasing pharmacologic and toxic effects
• Has no effect because only total concentration matters
• Causes irreversible drug sequestration in tissues

Correct Answer: Increases free drug fraction, potentially increasing pharmacologic and toxic effects

Q6. Which statement correctly describes the role of drug transporters (e.g., P‑glycoprotein, OATP) in variability of drug exposure?

• Transporters only affect topical drugs and not systemic therapy
• Transporter polymorphisms or inhibition/induction can change absorption, distribution and hepatic/renal clearance
• Transporters increase bioavailability for all drugs universally
• Transporters are irrelevant if a drug is highly lipophilic

Correct Answer: Transporter polymorphisms or inhibition/induction can change absorption, distribution and hepatic/renal clearance

Q7. Which age-related changes most commonly require dose adjustments in elderly patients?

• Increased hepatic and renal clearance with faster drug elimination
• Reduced renal and sometimes hepatic clearance with increased sensitivity to many drugs
• Complete loss of first-pass metabolism in all elderly individuals
• Marked increase in gut motility leading to decreased absorption

Correct Answer: Reduced renal and sometimes hepatic clearance with increased sensitivity to many drugs

Q8. When dosing in obesity, which approach best reflects current pharmacokinetic principles for loading and maintenance dosing?

• Use ideal body weight (IBW) for both loading and maintenance always
• Loading doses often scaled to total body weight (TBW); maintenance doses adjusted using lean or adjusted body weight
• Give fixed doses regardless of weight in obese patients
• Use body surface area only and ignore weight metrics

Correct Answer: Loading doses often scaled to total body weight (TBW); maintenance doses adjusted using lean or adjusted body weight

Q9. Which type of drug is the best candidate for therapeutic drug monitoring (TDM) to individualize dosing?

• Drugs with wide therapeutic index and predictable dose–response
• Drugs with narrow therapeutic index, significant PK variability, and a measurable concentration–effect relationship
• Topical creams with local effects only
• Drugs eliminated exclusively via expired air

Correct Answer: Drugs with narrow therapeutic index, significant PK variability, and a measurable concentration–effect relationship

Q10. What is the typical pharmacokinetic consequence of enzyme induction by a co-administered drug?

• Decreased metabolic clearance and increased plasma concentration of substrate drugs
• Increased metabolic clearance and decreased plasma concentration of substrate drugs
• No change in drug concentrations but increased half‑life
• Immediate allergic reactions unrelated to concentration

Correct Answer: Increased metabolic clearance and decreased plasma concentration of substrate drugs

Q11. How can food affect oral drug absorption and contribute to interindividual variability?

• Food has no effect on drug absorption for any oral medication
• Food composition (e.g., high‑fat meal) can increase absorption of lipophilic drugs or decrease absorption of others, altering bioavailability
• Food always reduces absorption regardless of drug properties
• Food converts all drugs into inactive metabolites in the gut

Correct Answer: Food composition (e.g., high‑fat meal) can increase absorption of lipophilic drugs or decrease absorption of others, altering bioavailability

Q12. A patient who is a CYP2D6 poor metabolizer receives codeine. What pharmacodynamic outcome would you expect?

• Increased conversion to morphine and exaggerated analgesia
• Poor conversion to morphine and reduced analgesic effect
• No change in response because codeine is inactive metabolically
• Excessive protein binding leading to toxicity

Correct Answer: Poor conversion to morphine and reduced analgesic effect

Q13. Which factor primarily reduces oral bioavailability (F) of a drug?

• High solubility in water only
• Extensive first‑pass hepatic metabolism and gut wall metabolism
• Increased renal clearance
• High plasma protein binding alone

Correct Answer: Extensive first‑pass hepatic metabolism and gut wall metabolism

Q14. For drug dosing in patients with reduced renal function, which creatinine‑based equation is most commonly referenced in dosing guidelines?

• Henderson–Hasselbalch equation
• Cockcroft–Gault equation for estimated creatinine clearance
• Body mass index formula
• Fick’s law of diffusion

Correct Answer: Cockcroft–Gault equation for estimated creatinine clearance

Q15. What is a principal advantage of population pharmacokinetic (popPK) modeling in dose individualization?

• It eliminates all variability so one dose fits everyone
• It identifies covariates (e.g., weight, age, renal function) that explain variability and informs dosing algorithms
• It requires no clinical data and is purely theoretical
• It only applies to intravenous fluids, not drugs

Correct Answer: It identifies covariates (e.g., weight, age, renal function) that explain variability and informs dosing algorithms

Q16. How does Bayesian forecasting improve individualized dosing during therapeutic drug monitoring?

• By solely using population averages and ignoring patient measurements
• By combining prior population PK data with a patient’s measured concentrations to estimate individualized PK parameters and optimal dose
• By replacing laboratory assays with predicted values only
• By always recommending halving the dose regardless of concentrations

Correct Answer: By combining prior population PK data with a patient’s measured concentrations to estimate individualized PK parameters and optimal dose

Q17. For maintenance dosing guided by TDM, why are trough concentrations commonly used?

• Trough concentrations are easier to correlate with steady‑state exposure and toxicity risk than random values
• Trough samples always overestimate the true exposure
• Peak concentrations are irrelevant for any drug
• Troughs avoid any variability caused by bioavailability

Correct Answer: Trough concentrations are easier to correlate with steady‑state exposure and toxicity risk than random values

Q18. How can poor adherence create the mistaken impression of altered pharmacokinetics in a patient?

• Nonadherence produces predictable steady therapeutic concentrations
• Irregular dosing causes unpredictable concentrations that may mimic increased clearance or treatment failure
• Nonadherence increases bioavailability uniformly
• Adherence has no impact on observed drug concentrations

Correct Answer: Irregular dosing causes unpredictable concentrations that may mimic increased clearance or treatment failure

Q19. In congestive heart failure, which pharmacokinetic change commonly affects drugs with high hepatic extraction ratios?

• Increased hepatic blood flow leading to increased clearance
• Reduced hepatic blood flow causing decreased clearance and increased drug exposure
• Complete blockade of renal excretion only
• Enhanced first‑pass metabolism decreasing bioavailability dramatically

Correct Answer: Reduced hepatic blood flow causing decreased clearance and increased drug exposure

Q20. Which of the following best describes interoccasion variability (IOV) and its implications for dose individualization?

• IOV is between‑subject variability and does not affect a single patient over time
• IOV arises from transient factors (illness, diet, interacting drugs) that change a patient’s PK profile across occasions and may require repeated TDM or adaptive dosing
• IOV is irrelevant once a steady dose is reached
• IOV can be eliminated by increasing the dose uniformly every day

Correct Answer: IOV arises from transient factors (illness, diet, interacting drugs) that change a patient’s PK profile across occasions and may require repeated TDM or adaptive dosing

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