PK Models + IV Bolus

Question 1

Pharmacokinetic Models

Answer 1

• Hypothesis using mathematical terms to concisely describe quantitative relationships
• Various models can be devised to stimulate the rate processes of ADME and make it possible to describe drug concentrations in the body as a function of time
• Most PK Models assume the plasma drug concentrations reflect tissue concentrations

Question 2

Models are used to… (7)

Answer 2

1. Predict plasma, tissue, and urine drug levels with any dosage regimen
2. Calculate the optimum dosage regimen for each patient individually
3. Estimate the possible accumulation of drugs and/or metabolites
4. Correlate drug concentrations with pharmacologic or toxicologic activity
5. Evaluate differences in bioavailability
6. Describe how changes in physiology or disease affect the ADME processes
7. Explain drug interactions

Question 3

Compartmental Models

Answer 3

• Attempt to relate plasma concentration to time data
• Body is described as a system consisting of a series of compartments
• Compartment is not a real physiologic region, but a tissue or group of tissues that behave kinetically homogeneously
• Since drugs are constantly moving in and out of compartments, rate constants are used to represent the movement of drugs

Question 4

Mammillary Models

Answer 4

• Most common
• Consists of one or more peripheral compartments connected to a central compartment
• Central compartment represents the plasma and higly perfused organs
• Usually n < 4

Question 5

Zero Order Kinetics

Answer 5

• Rate of reaction is independent of concentration of reactants
• Rate of reaction is proportional to the 0th power of the concentration
• Units: Concentration/time
• Zero order reactions are linear on a rectilinear graph

C = Co - Kt

Question 6

First Order Kinetics

Answer 6

• Rate of reaction is dependent on the concentration of reactants
• Rate of reaction is proportional to the 1st power of the concentration
• Units: time^(-1)
• First order reactions are linear are on a semi-log graph

lnC = lnCo - Kt
C = Co * e^(-Kt)

Question 7

IV Bolus Injection

Answer 7

• One-compartment model
• Upon injection, entire dose enters systemic circulation and distributes rapidly, results in dynamic equilibrium in the body
• Simplest model
• Body is a single homogeneous unit

Question 8

IV First Order Model Assumptions

Answer 8

• First-order kinetics

- Any change that occues in the plasma levels of drug reflects proportional changes in tissue levls

Question 9

IV First Order Model Advantages/Disadvantages

Answer 9

Advantages
1. Calculation of plasma drug concentration at any given time

Disadvantages

1. Requires multiple assumptions
2. Kinetic parameters do not have physiologic meaning
3. Data determines the model

Question 10

Derivation

Answer 10

dX/dt = -KX

X - amount of drug in body at any time t
K - apparent first-order elimination constant

Question 11

X =

Answer 11

Xo * e^(-kt)

lnX = ln(Dose) - Kt

Question 12

Plasma Drug Levels

Answer 12

lnC = LnCo - Kt
C = Co * e^(-Kt)

Co = drug concentration immediately after injection
-Graphed as lnC v.s. time

Question 13

Drug Concentrations by half lives

Answer 13

-0 = 100% of drug in body
-1 = 50% of drug in body
-2 = 25% of drug in body
-3 = 12.5% of drug in body
….etc.