Kinetics Exam 2

Linear PK

When elimination is first order, as the dose of drug increases, the plasma concentration and AUC increase proportionally

Non-linear PK

When an elimination process is saturated, any increase in drug dose results in a disproportionate increase in the plasma concentrations

What happens when a drug exhibits a non-linear PK?

The processes responsible for drug elimination are saturable at therapeutic concentrations

Mixed-order PK

Displaying first-order kinetics at low drug concentration and zero-order kinetics at high concentrations

What’s an example of a drug that switches order at therapeutic concentration?

Phenytoin

What’s an example of a drug that does NOT switch order until concentration reaches toxic range?

Theophylline

T/F: Linear pharmacokinetics means that the plot of plasma drug concentration versus time is a straight line.

False

Michaelis-Menten Kinetics

Model used to describe the kinetics of saturable enzyme systems

V_max

The theoretical maximum amount of drug that can be eliminated in a given period of time (amount/time)

K_m

Drug concentration when the rate of elimination is half the maximum rate (Michaelis constant; mass/volume or mg/L)

C

Total plasma drug concentration

What two factors determine V_max?

Quantity and efficiency of metabolizing enzymes

When plasma concentration is higher than Km, elimination approaches ____-order.

Zero-order

When plasma concentration is lower than Km, elimination approaches ____-order.

First-order

In Michaelis-Menton mode, when the rate of drug elimination proceeds at half the maximum rate, the drug concentration is known as:

a. V_max

b. K_m

c. ½ V_max

d. V_max C

b. K_m

T/F: At very high concentrations (higher than the drug’s K_m), drugs are more likely to exhibit first-order elimination.

False

At steady-state (after multiple doses)…

The rate of drug loss from the body (mg per day) = amount of drug administered (daily dose)

Drug accumulation in multiple drug dosing regimens happen when:

a. dosing interval is larger than elimination rate

b. dosing interval is smaller than elimination rate

c. dosing interval is longer than half-life of the drug

d. dosing interval is shorter than half-life of the drug

d. dosing interval is shorter than half-life of the drug

Steady state is reached in multiple drug dosing regimens when:

a. rate of administration = clearance

b. rate of administration = half-life of the drug

c. rate of administration = rate of elimination

d. rate of administration = elimination rate constant

c. rate of administration = rate of elimination

Non-linear PK means:

a. The plot of plasma drug concentration vs time after a dose is a straight line

b. The plot of dose vs exposure is a straight line

c. The plot of drug vs exposure is NOT a straight line

c. The plot of drug vs exposure is NOT a straight line

Which of the following defines “Mixed Order” PK?

a. Drug displays 1st order PK at low concentrations and zero order PK at high concentrations

b. Drug displays zero order PK at low concentrations and 1st order PK at high concentrations

c. Drug displays 1st and zero order PK regardless of the concentration

d. Drug only displays 1st order PK

a. Drug displays 1st order PK at low concentrations and zero order PK at high concentrations

In Michalis-Menton model, when the rate of drug elimination proceeds at half the maximum rate, the drug concentration is known as:

a. V_max

b. K_m

c. ½ V_max

d. V_max C

b. K_m

Which of the following PK parameters will determine the time to reach steady state?

a. Total daily dose

b. Elimination rate constant

c. Drug infusion rate constant

d. Apparent volume of distribution

b. Elimination rate constant

The oral absorption one-compartment PK model assumes all of the following assumptions EXCEPT:

a. If drug is 100% absorbed then F=1

b. Elimination rate is much greater than the absorption rate

c. Distribution to all tissues is instantaneous

d. Drug follows first-order elimination

b. Elimination rate is much greater than the absorption rate

Calculate the initial concentration of ampicillin (in mg/mL)  if the amount of ampicillin remaining in the body after 6 hrs was 20.8 mg, and the half-life of ampicillin is 1.3 hr.

509 mg/mL

A physician asks you to recommend a loading dose (in mg) and a constant rate iv infusion (in mg/hour) of a drug to rapidly achieve a steady state of 15 mg/L. The half-life of this drug is 6 hr, and the volume of distribution is 30 L.

• How much is your recommended loading dose (in mg)?

450 mg

A physician asks you to recommend a loading dose (in mg) and a constant rate iv infusion (in mg/hour) of a drug to rapidly achieve a steady state of 15 mg/L. The half-life of this drug is 6 hr, and the volume of distribution is 30 L.

• How much is your recommended constant rate iv infusion (in mg/hour)?

52.2 mg/h

A 80-kg, 30-year-old man is receiving phenytoin for the treatment of seizures. When this patient was taking a daily dose of 200 mg phenytoin, his steady state plasma concentration was 8.3 mg/L. Because, phenytoin plasma concentration was well below the therapeutic range, the patient’s daily dose was increased to 350 mg phenytoin, which resulted in a steady-state plasma concentration of 23 mg/L.

• Calculate the patient’s Vmax

• Calculate the patient’s Km

• 607.2 mg/day

• 16.9 mg/L