Inhibition of biliary excretion MCQs With Answer

Introduction: This quiz collection on inhibition of biliary excretion is designed for M.Pharm students studying Clinical Pharmacokinetics and Therapeutic Drug Monitoring. Biliary excretion, mediated by hepatic transporters such as BSEP, MRP2 and OATP families, plays a critical role in elimination of many drugs and metabolites. Inhibition of these transport pathways can alter systemic exposure, precipitate drug–drug interactions, and cause cholestatic liver injury. These 20 carefully constructed MCQs explore mechanistic aspects, kinetic consequences, common inhibitory drugs, in vitro/in vivo assessment methods, clinical monitoring, and regulatory considerations. Use these questions to deepen understanding of transporter-mediated clearance and implications for safe, effective drug therapy.

Q1. What is the primary consequence on systemic plasma exposure when biliary excretion of a drug that contributes 50% of total clearance is completely inhibited?

• Plasma AUC decreases by 50%
• Plasma AUC remains unchanged
• Plasma AUC doubles
• Plasma half-life decreases

Correct Answer: Plasma AUC doubles

Q2. Which hepatic transporter is most directly responsible for canalicular bile salt export and is commonly implicated in drug-induced cholestasis when inhibited?

• OATP1B1
• BSEP (ABCB11)
• OAT2
• PEPT1

Correct Answer: BSEP (ABCB11)

Q3. According to the well-stirred model, hepatic clearance (CLh) is determined by which of the following relationships?

• CLh = Qh + fu × CLint
• CLh = (Qh × fu × CLint) / (Qh + fu × CLint)
• CLh = fu / CLint
• CLh = CLint / Qh

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

Q4. Which in vitro system is most commonly used to evaluate biliary transporter-mediated efflux and predict in vivo inhibition of biliary excretion?

• Isolated renal tubules
• Sandwich-cultured human hepatocytes
• Intestinal Caco-2 monolayers
• Red blood cell hemolysis assay

Correct Answer: Sandwich-cultured human hepatocytes

Q5. In competitive inhibition of a canalicular transporter, which kinetic parameter is primarily affected in a Michaelis–Menten framework?

• Vmax decreases, Km unchanged
• Both Vmax and Km increase
• Km increases, Vmax unchanged
• Vmax increases, Km decreases

Correct Answer: Km increases, Vmax unchanged

Q6. Which clinical laboratory marker is most specific for cholestatic impairment due to inhibited biliary excretion?

• Serum creatinine
• Serum alkaline phosphatase (ALP)
• Serum amylase
• Serum troponin

Correct Answer: Serum alkaline phosphatase (ALP)

Q7. Which drug is a well-known inhibitor of OATP1B1 and can reduce biliary uptake of certain statins, causing increased systemic exposure?

• Rifampicin (single-dose effect)
• Metformin
• Furosemide
• Acetaminophen

Correct Answer: Rifampicin (single-dose effect)

Q8. Which transporter genetic polymorphism would most directly alter biliary excretion mediated by OATP uptake into hepatocytes?

• SLCO1B1 polymorphism
• CFTR mutation
• SLC6A4 polymorphism
• VKORC1 variant

Correct Answer: SLCO1B1 polymorphism

Q9. If a drug’s biliary clearance (CLbile) is a major route and an interacting drug causes noncompetitive inhibition of the canalicular transporter, what is the expected change in Vmax and Km for biliary transport?

• Vmax decreases, Km unchanged
• Km increases, Vmax unchanged
• Vmax increases, Km decreases
• Both Vmax and Km increase

Correct Answer: Vmax decreases, Km unchanged

Q10. Which of the following clinical consequences is most likely when biliary excretion of bile acids is inhibited?

• Nephrotic syndrome
• Cholestatic liver injury with pruritus and jaundice
• Acute pancreatitis
• Hypoglycemia without liver injury

Correct Answer: Cholestatic liver injury with pruritus and jaundice

Q11. Which drug was withdrawn from the market partly due to BSEP inhibition–associated liver toxicity?

• Troglitazone
• Metoprolol
• Ibuprofen
• Omeprazole

Correct Answer: Troglitazone

Q12. For a low-extraction drug (hepatic extraction ratio <<1) primarily cleared by biliary excretion, inhibition of transporter-mediated biliary clearance will most strongly affect which parameter?

• Renal clearance only
• Systemic bioavailability during IV dosing
• Systemic clearance and AUC
• Volume of distribution without affecting clearance

Correct Answer: Systemic clearance and AUC

Q13. Which regulatory recommendation is commonly applied when assessing risk of transporter-mediated inhibition of biliary excretion during drug development?

• Ignore in vitro transporter data if phase I shows tolerability
• Perform in vitro transporter inhibition assays and, if positive, follow with predictive modelling or clinical DDI studies
• Only study renal transporters; hepatic transporters are irrelevant
• Test transporter inhibition only after product approval

Correct Answer: Perform in vitro transporter inhibition assays and, if positive, follow with predictive modelling or clinical DDI studies

Q14. Which experimental assay directly measures ATP-dependent transport activity of canalicular ABC transporters like BSEP and MRP2?

• ATPase activity assay or membrane vesicle transport assay
• Plasma protein binding assay
• HPLC impurity profiling
• Glucose uptake assay

Correct Answer: ATPase activity assay or membrane vesicle transport assay

Q15. Probenecid is classically known for inhibiting renal OATs; which additional effect relevant to biliary excretion has been reported in transporter studies?

• Activation of BSEP-mediated bile salt export
• Inhibition of certain MRP-mediated efflux pathways
• Enhancement of intestinal absorption of macromolecules
• Inhibition of CYP3A4 enzyme at therapeutic concentrations

Correct Answer: Inhibition of certain MRP-mediated efflux pathways

Q16. In drug–drug interaction prediction, the unbound hepatic inlet concentration (Iin,u) is used because:

• Only unbound drug can interact with hepatic transporters to inhibit biliary uptake or efflux
• Total plasma concentration always underestimates inhibition risk
• It ignores protein binding which is irrelevant in transporter interactions
• Iin,u is identical to systemic steady-state concentration

Correct Answer: Only unbound drug can interact with hepatic transporters to inhibit biliary uptake or efflux

Q17. Which transporter primarily mediates canalicular excretion of conjugated bilirubin and is relevant to bilirubin elevation when inhibited?

• MRP2 (ABCC2)
• OATP2B1
• P-gp (ABCB1)
• GLUT2

Correct Answer: MRP2 (ABCC2)

Q18. A new drug shows potent inhibition of BSEP in vesicle assays at clinically relevant concentrations. Which early clinical monitoring strategy is most appropriate in phase I studies?

• Frequent ECG monitoring only
• Serial measurement of hepatic enzymes, bilirubin and bile acid profiles
• Urinalysis for glucose and ketones only
• No monitoring is needed for transporter inhibition

Correct Answer: Serial measurement of hepatic enzymes, bilirubin and bile acid profiles

Q19. Which mathematical relationship best describes how AUC changes if total clearance is reduced by 40% due to inhibited biliary excretion (assuming linear kinetics and unchanged bioavailability)?

• AUC decreases by 40%
• AUC increases by 67%
• AUC increases by 40%
• AUC remains unchanged

Correct Answer: AUC increases by 67%

Q20. Which clinical example best illustrates transporter-mediated drug interactions affecting biliary excretion and systemic exposure?

• Grapefruit juice inhibiting intestinal CYP3A4 causing increased felodipine levels
• Ciclosporine inhibiting OATP and BSEP leading to increased plasma exposure of certain statins and risk of liver injury
• Loop diuretics causing hyperkalemia by renal loss
• Beta-blockers causing bronchospasm in asthmatics

Correct Answer: Ciclosporine inhibiting OATP and BSEP leading to increased plasma exposure of certain statins and risk of liver injury

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