Organ extraction and hepatic clearance models MCQs With Answer

Organ extraction and hepatic clearance models MCQs With Answer

This quiz set is designed for M.Pharm students studying Clinical Pharmacokinetics and Therapeutic Drug Monitoring. It focuses on organ extraction concepts and the major hepatic clearance models (well-stirred, parallel-tube, and dispersion), covering definitions, key equations, assumptions, IVIVE scaling, transporter effects, and practical implications for high- and low-extraction drugs. Questions include conceptual items and calculation examples to strengthen understanding of determinants of hepatic clearance — hepatic blood flow, intrinsic clearance, and fraction unbound — and the limitations of each model. Answers are provided for rapid self-assessment and revision for advanced coursework and exams.

Q1. What is the hepatic extraction ratio (E) defined as?

• The fraction of drug removed by the liver per unit time
• The fraction of drug entering the liver that is removed during a single pass
• The ratio of hepatic clearance to intrinsic clearance
• The difference between arterial and venous concentrations divided by venous concentration

Correct Answer: The fraction of drug entering the liver that is removed during a single pass

Q2. Which equation correctly relates hepatic clearance (CLh) to hepatic blood flow (Qh) and extraction ratio (E)?

• CLh = Qh / E
• CLh = Qh × E
• CLh = E / Qh
• CLh = Qh + E

Correct Answer: CLh = Qh × E

Q3. According to the well-stirred (venous equilibrium) model, which expression gives hepatic clearance?

• CLh = Qh × E
• CLh = Qh × (fu × Clint) / (Qh + fu × Clint)
• CLh = fu × Clint
• CLh = Qh × ln(1 + fu × Clint / Qh)

Correct Answer: CLh = Qh × (fu × Clint) / (Qh + fu × Clint)

Q4. For a drug with a high hepatic extraction ratio (E ≈ 0.8–1.0), which factor primarily determines hepatic clearance?

• Fraction unbound (fu)
• Intrinsic clearance (Clint)
• Hepatic blood flow (Qh)
• Plasma protein binding affinity

Correct Answer: Hepatic blood flow (Qh)

Q5. For a low-extraction drug, which parameters mainly control hepatic clearance?

• Hepatic blood flow only
• Fraction unbound (fu) and intrinsic clearance (Clint)
• Distribution volume and half-life
• Renal excretion fraction

Correct Answer: Fraction unbound (fu) and intrinsic clearance (Clint)

Q6. Which statement best characterizes the parallel-tube model of hepatic elimination?

• The liver is considered a single well-mixed compartment with instantaneous equilibrium
• The liver is modeled as many parallel tubular sinusoids with axial concentration decline along each tube
• The model ignores blood flow and focuses solely on intrinsic clearance
• The model assumes there’s no protein binding in blood

Correct Answer: The liver is modeled as many parallel tubular sinusoids with axial concentration decline along each tube

Q7. How is intrinsic clearance (Clint) usually defined in hepatic pharmacokinetics?

• The clearance limited by hepatic blood flow
• The inherent ability of hepatic enzymes and transporters to eliminate unbound drug, often estimated in vitro as Vmax/Km
• The fraction of drug escaping first-pass metabolism
• The product of hepatic blood flow and extraction ratio

Correct Answer: The inherent ability of hepatic enzymes and transporters to eliminate unbound drug, often estimated in vitro as Vmax/Km

Q8. Hepatic bioavailability (Fh) for an orally administered drug is related to extraction ratio (E) by which relation (neglecting gut metabolism)?

• Fh = E
• Fh = 1 + E
• Fh = 1 − E
• Fh = Qh × E

Correct Answer: Fh = 1 − E

Q9. Which scaling approach is commonly used to extrapolate microsomal intrinsic clearance to whole liver intrinsic clearance in IVIVE?

• Multiply microsomal Clint by plasma protein binding
• Multiply microsomal Clint by microsomal protein per gram liver (MPPGL) and liver weight
• Divide microsomal Clint by hepatic blood flow
• Multiply microsomal Clint by renal clearance

Correct Answer: Multiply microsomal Clint by microsomal protein per gram liver (MPPGL) and liver weight

Q10. Which assumption is central to the well-stirred model and often criticized as a limitation?

• The liver has no blood flow
• The liver is instantaneously and homogeneously mixed so outflow concentration equals liver tissue concentration
• Drug elimination occurs only in the blood and not in hepatocytes
• The model requires explicit inclusion of transporter kinetics

Correct Answer: The liver is instantaneously and homogeneously mixed so outflow concentration equals liver tissue concentration

Q11. Using the well-stirred model, calculate hepatic clearance (CLh) given Qh = 90 L/hr, fu = 0.1, and Clint = 200 L/hr.

• Approximately 180 L/hr
• Approximately 16.4 L/hr
• Approximately 90 L/hr
• Approximately 2 L/hr

Correct Answer: Approximately 16.4 L/hr

Q12. If arterial concentration (Ca) entering the liver is 10 mg/L and hepatic venous concentration (Cv) leaving the liver is 2 mg/L, what is the extraction ratio (E)?

• 0.2
• 0.8
• 5.0
• 0.5

Correct Answer: 0.8

Q13. What unique feature does the dispersion model include compared with the well-stirred and parallel-tube models?

• It ignores intrinsic clearance
• It includes an axial dispersion parameter to represent incomplete mixing along the sinusoid
• It treats the liver as a single point with no spatial variation
• It assumes instant transporter-mediated uptake only

Correct Answer: It includes an axial dispersion parameter to represent incomplete mixing along the sinusoid

Q14. How does high plasma protein binding generally affect hepatic clearance of a low-extraction drug?

• It increases clearance because bound drug is preferentially cleared
• It decreases clearance because only the unbound fraction is available for hepatic metabolism
• It has no effect on clearance regardless of extraction ratio
• It converts the drug into a high-extraction drug

Correct Answer: It decreases clearance because only the unbound fraction is available for hepatic metabolism

Q15. Which clinical or experimental measure is commonly used as a proxy for hepatic blood flow?

• Creatinine clearance
• Indocyanine green (ICG) plasma disappearance or clearance
• Serum albumin concentration
• Urinary excretion of unchanged drug

Correct Answer: Indocyanine green (ICG) plasma disappearance or clearance

Q16. Inhibition of hepatic uptake transporters (e.g., OATP) most directly results in which effect on hepatic clearance for uptake-limited drugs?

• Increase in hepatic clearance
• No change in hepatic clearance
• Decrease in hepatic clearance due to reduced intracellular availability for metabolism
• Conversion of the drug to a high-extraction drug

Correct Answer: Decrease in hepatic clearance due to reduced intracellular availability for metabolism

Q17. When scaling hepatocyte-derived intrinsic clearance to whole-organ clearance, which physiological scaling factor is essential?

• Microsomal protein per gram liver (MPPGL)
• Hepatocellularity per gram liver (number of hepatocytes per g liver)
• Plasma protein concentration
• Renal blood flow

Correct Answer: Hepatocellularity per gram liver (number of hepatocytes per g liver)

Q18. If a drug’s hepatic clearance approximates hepatic blood flow (CLh ≈ Qh), how would the drug be classified?

• Low-extraction drug
• High-extraction drug (flow-limited)
• Renally eliminated drug
• Protein-bound only drug with no hepatic metabolism

Correct Answer: High-extraction drug (flow-limited)

Q19. Which limitation applies to using the well-stirred model for drugs subject to transporter-mediated uptake or highly zonal metabolism?

• The model overestimates renal clearance
• The assumption of homogeneous liver concentration and instantaneous equilibrium may be invalid, leading to inaccurate predictions
• The model ignores blood flow entirely
• The model requires separate microsomal scaling factors for kidney

Correct Answer: The assumption of homogeneous liver concentration and instantaneous equilibrium may be invalid, leading to inaccurate predictions

Q20. What is the expected effect of strong enzyme induction (large increase in Clint) on hepatic clearance for a drug initially classified as low-extraction?

• Clearance will remain unchanged because the drug is flow-limited
• Clearance will likely increase markedly because Clint is a limiting factor for low-extraction drugs
• Clearance will decrease due to saturation of transporters
• Clearance becomes solely dependent on plasma protein binding

Correct Answer: Clearance will likely increase markedly because Clint is a limiting factor for low-extraction drugs

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