Kinetics Exam 1

As dose increases, what happens to plasma drug concentration?

increases

What is the relationship between clearance and rate of elimination?

proportional

What are factors that can change plasma drug levels on an individual level?

age, disease, diet, environment, drug interactions, genetics

If a person has renal failure, how will their plasma drug concentrations be?

higher

If a person has kidney hyperactivity, how will this affect plasma drug concentration?

lower

When are optimum dosing regimes determined?

during drug development process

Why do we need to measure drug concentrations in order to determine?

how rapidly the drug appears in the blood after admin, how the drug leaves the body and how its concentration changes over time, how fast the drug disappears as is metabolized

What are invasive ways to measure drug concentrations?

blood, tissue biopsies

What are noninvasive methods to measure drug concentrations?

urine, saliva

What is the most commonly used sample for measurement of drug levels?

plasma

Changes in plasma drug will typically reflect changes in what part of the body?

tissue

What is the onset time for measuring drug concentrations?

time at which the drug starts to work or reaches MEC

What is the intensity when it comes to measuring drug plasma concentrations?

range between peak plasma level and MEC

What is the duration when it comes to measuring drug plasma concentrations?

time period at which drug is above MEC

What is the therapeutic range?

concentration between MEC and MTC

How are absorption and elimination related at peak plasma concentration?

equal

When do specific ADME processes occur?

simultaneously

What are the primary PK parameters and what do they depend on?

dose - D, bioavailability - F, volume of distribution - Vd, clearance - Cl, absorption rate constant - ka

What are the secondary PK parameters?

AUC, k

What are the tertiary Pk parameters?

tmax, Cmax, t1/2

What is the type of model is it where it used perfusion or blood flow models and are very good at predicting tissue drug concentrations?

physiological model

What is the velocity with which the reaction occurs?

rate

What is the way in which the concentration of a drug affects the rate of a reaction?

order

What relates concentration of a drug with time?

rate constant

How is drug concentration C in a zero-order reaction?

decreasing at a constant rate

What are some examples of zero-order reactions?

drug degradation, drug absorption from a controlled-release oral dosage form, saturable processes

What are some examples of zero order saturable processes?

binding to proteins, biotransformation, drug transport, active tubular drug secretion

How is drug concentration changing in a first order reaction?

decreasing at a rate proportional to the amount of drug remaining

What order is drug absorption from an immediate-release oral dosage form?

first

What order is drug elimination from tissues?

first order

What is the period of time required for the concentration of drug to decreased by one half?

half life

How is the half life for first order reactions?

constant

For zero order reactions how is half life?

not constant

What is half life proportional to for a zero order reaction?

C

How is frequency of admin effected for drugs with longer half lifes?

less frequent dosing

Which compartment model describes instantaneous distribution?

one-compartment open model

What is an IV bolus?

a single dose of drug admined by rapid IV

What does the rate of elimination depend for most drugs?

k and Db

What is the importance of the elimination rate constant k clinically?

helps determine dosing and frequency of admin

What is a proportionality factor that relates the total amount of drug in the body to the concentration of drug measured?

Vd

What are the units of k?

h-1

What are the units of Vd?

L

What is the size of a compartment necessary to account for the total quantity of the drug in the body, if it were present throughout the body at the same concentration found in plasma?

Vd

Vd indicates the extent of drug _____

distribution

What is the plasma volume?

7.5 L

When is the drug mostly in the plasma in regard to Vd?

Vd less than or equal to 7.5 L

When is the drug present in the plasma and tissues or fluids outside plasma in regard to Vd?

Vd > 7.5 L

When is the drug mostly in the tissues in regard to Vd?

Vd > 10,000 L

What do increases in tissue binding or lipophilicity lead to in regards to Vd?

increases

What do increases in plasma protein binding or hydrophilicity lead to for Vd?

decreases

What is the clinical importance of Vd?

allows for calculation of the loading dose, expected Cp after admin

What are the two ways drug elimination can be described?

rate of elimination, clearance

What is the amount eliminated per unit time?

rate of elimination

What does the rate of elimination depend on for zero order drugs?

constant

What is the volume of plasma from which drug is removed over time?

clearance

If there is an increased Cp, what does that mean for elimination rate?

increased

How is clearance for first-order drugs?

constant, regardless of drug concentration

How is clearance for zero order drugs?

not constant

What is the sum of all organ clearances?

total body clearance

What is does total body clearance help determine for dosing?

maintenance dose and frequency of admin

When there is a decreased ClT what does that mean for rate of elimination?

decreased

What is creatinine clearance?

measure of kidney function

What does the AUC indicate?

drug bioavailability

What does the multicompartment model allow us to determine?

how much of dose is eliminated, how much drug remains in plasma, how much drug accumulates in tissues

What is the distribution phase of the two compartment model?

kidney or liver getting rid of drug and going into compartment 2

When does tissue drug concentration reach maximum for the 2-compartment model?

distributive equilibrium

How do the plasma and tissue concentrations decline for the two compt. model?

parallel

In the elimination phase, what does plasma drug concentration indicate?

tissue drug concentration

What is Vp, Vc, or Vi?

distribution phase

What is (Vd)ss?

distribution equilibrium

What is (Vd)B?

volume of distribution when drug is in elimination phase

What does Dt estimate?

drug accumulation in tissues, chronic toxicity

What does Dt relate duration of pharmacological activity to?

dose

What is the 3-compartment model for IV bolus and how does drug distribute?

additional deep tissue; very slowly to this compartment

What are the factors affecting choice of compartment model?

route of admin, rate of drug absorption, total time for blood sampling, sensitivity of the assay

If drug is taken IV bolus, what model will it follow?

2 compartment

For drugs with a short distribution phase, how is there distribution within the central compartment?

rapid

For drug with a short distribution phase how is there distribution to tissues?

limited

How could a drug with a short distribution phase be described?

one-compartment modle

What kind of drugs is the distribution phase important for?

high target plasma concentration, close to distributive phase, short elimination phase

What does a steep distribution phase lead to greater risks of?

ADRs