Pharmacokinetics and Drug Metabolism Flashcards

A drug has a half-life of 8 hours and follows first-order kinetics. Approximately how long does it take to reach steady-state plasma concentration when administered at regular dosing intervals?

Answer: 40 hours (five half-lives)

For first-order kinetics, steady-state is achieved after approximately 4–5 half-lives regardless of dose or dosing interval. With a half-life of 8 hours, steady-state is reached in approximately 5 × 8 = 40 hours.

A patient with severe renal impairment (CrCl < 15 mL/min) is prescribed a drug that is 90% renally eliminated unchanged. Which dosing adjustment is MOST appropriate?

Answer: Reduce the dose and/or extend the dosing interval to prevent drug accumulation

Drugs highly dependent on renal elimination accumulate in patients with renal impairment because the kidneys cannot clear the drug efficiently. The dose must be reduced and/or the interval extended to maintain safe plasma concentrations and avoid toxicity.

Which cytochrome P450 enzyme is responsible for metabolizing the greatest number of clinically used drugs, making it the most clinically significant source of drug-drug interactions?

Answer: CYP3A4

CYP3A4 is the most abundant CYP enzyme in the liver and intestine and metabolizes approximately 50% of clinically used drugs. It is the most common source of pharmacokinetic drug-drug interactions through induction or inhibition.

A pharmacist calculates that a drug has a volume of distribution (Vd) of 500 L in a 70 kg patient. What does this large Vd indicate?

Answer: The drug is extensively distributed into peripheral tissues or fat

A large Vd (much greater than total body water of ~42 L) indicates that the drug distributes extensively outside the plasma into peripheral tissues, body fat, or binds intracellularly. Small Vd values suggest the drug stays primarily in the plasma.

A patient is taking phenytoin, which follows zero-order (saturable) kinetics at therapeutic doses. How does this differ from first-order kinetics in clinical practice?

Answer: A fixed amount of drug is eliminated per unit time; small dose increases can cause disproportionately large rises in plasma concentration

Zero-order (saturable) kinetics means the metabolic enzymes are saturated; a constant amount (not proportion) is eliminated per unit time. Small dose increases in the therapeutic range can cause dramatic, disproportionate increases in plasma levels, significantly raising toxicity risk with phenytoin.

A patient with hepatic cirrhosis requires a drug that undergoes extensive first-pass metabolism. How does cirrhosis typically affect the bioavailability of this drug?

Answer: Bioavailability increases because first-pass metabolism is reduced, allowing more drug to reach systemic circulation

First-pass metabolism occurs in the liver before a drug reaches systemic circulation. In hepatic cirrhosis, functional liver mass is reduced and portosystemic shunting bypasses the liver, significantly reducing first-pass metabolism and increasing bioavailability — potentially to toxic levels.