Introduction: The two-compartment open model is a core pharmacokinetic concept describing drugs that distribute rapidly into a central compartment (blood and well-perfused tissues) and more slowly into a peripheral compartment (less-perfused tissues). Key concepts include microconstants (k12, k21, k10), macroconstants (alpha, beta), biexponential plasma concentration equation Cp = A e-alpha t + B e-beta t, volumes (Vc, Vss), clearance (CL), AUC, and the method of residuals for parameter estimation. Understanding distribution and elimination phases, half-lives, and relationships among parameters helps in dosage design, interpretation of concentration–time profiles, and therapeutic monitoring. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What structural compartments define the two-compartment open model?
- Central compartment and peripheral compartment
- Blood compartment and renal compartment
- Liver compartment and tissue compartment
- Single homogeneous compartment only
Correct Answer: Central compartment and peripheral compartment
Q2. Which equation represents plasma concentration versus time after an IV bolus in a two-compartment open model?
- Cp = A e-alpha t + B e-beta t
- Cp = C e-kt
- Cp = Dose / V
- Cp = k12·t + k21·t
Correct Answer: Cp = A e-alpha t + B e-beta t
Q3. In biexponential decline, what do the macroconstants alpha and beta represent?
- Alpha = distribution rate constant (faster phase); Beta = elimination rate constant (slower phase)
- Alpha = absorption rate constant; Beta = renal flow
- Alpha = clearance; Beta = volume of distribution
- Alpha and beta are both absorption constants
Correct Answer: Alpha = distribution rate constant (faster phase); Beta = elimination rate constant (slower phase)
Q4. Which of the following are microconstants in the two-compartment open model?
- k12, k21, k10
- Alpha, beta
- Vc, Vss
- A, B
Correct Answer: k12, k21, k10
Q5. For an IV bolus two-compartment model, how is the apparent central volume of distribution (Vc) calculated from A and B?
- Vc = Dose / (A + B)
- Vc = A / alpha + B / beta
- Vc = CL / beta
- Vc = k12 / k21
Correct Answer: Vc = Dose / (A + B)
Q6. How is total body clearance (CL) most generally calculated from dose and exposure for an IV bolus?
- CL = Dose / AUC
- CL = Vc · k12
- CL = A + B
- CL = alpha · beta
Correct Answer: CL = Dose / AUC
Q7. What is the expression for AUC (area under the plasma concentration–time curve) after an IV bolus in a two-compartment model?
- AUC = A/alpha + B/beta
- AUC = Dose / Vc
- AUC = alpha + beta
- AUC = k12 + k21 + k10
Correct Answer: AUC = A/alpha + B/beta
Q8. How is the terminal elimination half-life (t1/2β) related to the macroconstant beta?
- t1/2β = ln 2 / beta
- t1/2β = beta / ln 2
- t1/2β = ln 2 / alpha
- t1/2β = A / B
Correct Answer: t1/2β = ln 2 / beta
Q9. Which formula represents the volume of distribution at steady state (Vss) in terms of Vc and microconstants?
- Vss = Vc × (1 + k12/k21)
- Vss = Dose / A
- Vss = A/alpha + B/beta
- Vss = CL / beta
Correct Answer: Vss = Vc × (1 + k12/k21)
Q10. Which technique is commonly used to separate the distribution and elimination phases graphically?
- Method of residuals (feathering)
- HPLC assay
- Mass balance study
- Single-point sampling
Correct Answer: Method of residuals (feathering)
Q11. What pattern is typically seen on a semi-log plot of plasma concentration vs time for a two-compartment drug after IV bolus?
- Two linear phases: an initial steep decline followed by a shallower terminal slope
- Single straight line throughout
- Oscillating peaks and troughs only
- Immediate plateau with no decline
Correct Answer: Two linear phases: an initial steep decline followed by a shallower terminal slope
Q12. At t = 0 after an IV bolus in a two-compartment model, what is the relationship among A, B, Dose and Vc?
- A + B = Dose / Vc
- A = Dose / Vss
- B = CL / Vc
- A × B = Dose
Correct Answer: A + B = Dose / Vc
Q13. Which microconstant represents the elimination (clearance) from the central compartment?
- k10
- k12
- k21
- alpha
Correct Answer: k10
Q14. When is a two-compartment model more appropriate than a one-compartment model?
- When drug shows rapid distribution phase followed by slower elimination phase
- When drug is confined strictly to plasma only
- When absorption is zero-order only
- When there is no detectable distribution phase
Correct Answer: When drug shows rapid distribution phase followed by slower elimination phase
Q15. What is the relationship between clearance (CL), the central volume (Vc) and microconstant k10?
- CL = k10 × Vc
- CL = Vc / k10
- CL = k12 + k21
- CL = A + B
Correct Answer: CL = k10 × Vc
Q16. Which coefficient (A or B) is primarily associated with the rapid distribution phase contribution in the biexponential equation?
- A
- B
- Neither; both represent elimination only
- Alpha, not A or B
Correct Answer: A
Q17. Which statement is generally true about the magnitudes of alpha and beta in a two-compartment model?
- Alpha is larger than beta (alpha > beta)
- Alpha equals beta
- Alpha is smaller than beta (alpha < beta)
- Alpha and beta are negative values
Correct Answer: Alpha is larger than beta (alpha > beta)
Q18. Which parameter best describes the overall extent of distribution of a drug among body compartments?
- Vss (volume of distribution at steady state)
- Alpha
- k10 only
- Method of residuals
Correct Answer: Vss (volume of distribution at steady state)
Q19. For a drug given by constant IV infusion, how is steady-state plasma concentration (Css) determined regardless of compartment number?
- Css = Rate of infusion / CL
- Css = Dose / Vc
- Css = A/alpha + B/beta
- Css = k12 / k21
Correct Answer: Css = Rate of infusion / CL
Q20. What is the first practical step in the method of residuals (feathering) to analyze biexponential data?
- Identify the terminal elimination slope (beta), extrapolate it back, and subtract from observed data to obtain residuals
- Calculate Vss directly from A and B without plotting
- Measure urine output only
- Assume a one-compartment model and ignore early points
Correct Answer: Identify the terminal elimination slope (beta), extrapolate it back, and subtract from observed data to obtain residuals
Q21. Which microconstant primarily governs the initial rapid fall in plasma concentration after an IV bolus?
- k12 (transfer from central to peripheral)
- k10 (elimination only)
- k21 (transfer from peripheral to central)
- beta
Correct Answer: k12 (transfer from central to peripheral)
Q22. In the standard two-compartment open model, which statement about the peripheral compartment is correct?
- Peripheral compartment exchanges drug with the central compartment but does not directly eliminate drug
- Peripheral compartment is the site of primary elimination only
- Peripheral compartment receives drug only by metabolism
- Peripheral compartment is identical to the central compartment
Correct Answer: Peripheral compartment exchanges drug with the central compartment but does not directly eliminate drug
Q23. Which phase of the biexponential curve is used to determine the elimination half-life relevant for dosing interval decisions?
- The terminal (beta) phase
- The initial (alpha) phase
- Neither; use microconstants only
- Only the peak concentration matters
Correct Answer: The terminal (beta) phase
Q24. Which data analysis method fits both A, B, alpha and beta simultaneously using all concentration–time points?
- Non-linear regression (curve fitting)
- Graphical method only
- Urine collection method
- Radioisotope scanning
Correct Answer: Non-linear regression (curve fitting)
Q25. If k21 (peripheral → central) increases while other parameters remain constant, what happens to Vss?
- Vss decreases
- Vss increases
- Vss remains unchanged
- Vss becomes infinite
Correct Answer: Vss decreases
Q26. Clinically, a large Vss indicates which of the following?
- Extensive distribution of drug into tissues
- Poor tissue penetration
- High renal clearance only
- Rapid elimination from plasma only
Correct Answer: Extensive distribution of drug into tissues
Q27. In the standard two-compartment open model, elimination occurs from which compartment?
- Central compartment
- Peripheral compartment only
- Both compartments equally
- No elimination occurs in this model
Correct Answer: Central compartment
Q28. When calculating a loading dose for a rapidly distributing two-compartment drug aiming to rapidly achieve target plasma concentration, which volume should be used?
- Vc (central volume of distribution)
- Vss (steady-state volume)
- AUC
- k10 only
Correct Answer: Vc (central volume of distribution)
Q29. For a typical two-compartment IV bolus profile, are the coefficients A and B generally positive or negative?
- Positive
- Negative
- One is positive and one is negative always
- They are complex numbers
Correct Answer: Positive
Q30. Which practical consideration arises from a pronounced distribution (alpha) phase when initiating therapy?
- Loading doses may be needed and sampling too early can mislead apparent clearance estimates
- Oral bioavailability becomes zero
- Renal dosing adjustments are irrelevant
- Drug can be dosed solely based on Vss without regard to clearance
Correct Answer: Loading doses may be needed and sampling too early can mislead apparent clearance estimates
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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