E1 L1: IV Bolus Flashcards
PK definition
The study of the process by which a drug is absorbed, distributed, metabolized, and excreted by the body (what the BODY does to the DRUG)
ADME
Absorption (Small intestine)
Metabolism (Liver)
Distribution (Systemic circulation)
Excretion (Kidney, other tissues)
Two major elimination pathways
Hepatic metabolism
Renal excretion
PK goal
Optimal drug therapy - determination of optimal dosage regimen, e.g. how many mg and how many times a day
- is our window to the body in pK
Blood
IV bolus purpose
Rapid injection - ensures that the entire dose enters the systemic circulation Immediately
One compartment model assumptions
Body acts like a single homogeneous compartment and drug rapidly distributes uniformly in it
The drug is in rapid equilibrium between the blood and the tissues
Changes in the plasma concentration of drug will result in proportional changes in tissue drug levels
1 compartment model use
Blood compartment alone is sufficient to explain drug disposition
Multi-compartment model
One (blood) compartment alone is not sufficient to explain drug disposition. More than one (ie. multi) compartments are needed
First order elimination
Elimination rate is proportional to the concentration (or amount of drug)
Ex: time: 1, amount eliminated 10, amount remaining, 90
Time 2: amount eliminated - 9, Amount remaining - 81, etc.
Elimination rate constant (Kel)
Kel is the proportionality constant relating the rate of elimination and the amount of drug in the body
A drug specific property
Has units of time-1, eg. min or h-1
Volume of distribution (Vd)
Vd is the proportionality constant relating the amount of drug in the body and drug concentration in plasma
IMMEDIATELY after an IV bolus dose,
A drug specific property
Has units of volume (mL, L)
Q: 100mg of drug X admin via IV bolus. What would be the typically expected drug conc. in the blood taken right after the IV dose?
(Body Weight: 60Kg)
Blood Volume (5L)
A. 100 mg/5L = 20mg/L
B. >20mg/L
C. <20 mg/L
C: <20mg/L
Most drugs exhibit tissue distribution, starting immediately after the IV dose
Different drugs show different - After a given dose, thus a different VD
CP0
Hydrophilic compounds
Do NOT cross lipid bilayers readily
Higher C0 given a dose
Lipophilic compounds
Better tissue distribution
Lower C0 given a dose
Vd is a measure of
Drug distribution in the body
One compartment IV bolus model equation
CP = Cp0 -e^-kt
The proportionality constant relating the rate of drug elimination and the plasma concentration
Clearance (CL)
Kel Vs CL
Large Kel = Large Clearance
Both tell us about drug elimination
Represents the fractional rate of loss of drug from the body
Kel
Kel vs CL (in depth explain)
Kel - fractional rate of drug loss from the body
CL - Volume of drug-containing plasma from which drug is COMPLETELY cleared
Can CL exceed cardiac output
No (because drugs reach the drug-eliminating organs via the blood pumped by heart)
T/F: Kel has a limit it can exceed
False - it has no limit that it can exceed
Linear kinetics
If we double the dose, then the plasma concentration will double at each time point (straight line)
Non-linear kinetics properties
Dose-dependent pk
It occurs when one (or more) of ADME processes shows saturation
Non-linear kinetics ex
Hepatic metabolism of a drug is saturated in typical dose range
Non-linear kinetics pharmacokinetic parameters are…
Dose dependent (CL and VD)
Linear Q:
For a drug that has linear kinetics, if we double the dose, then the plasma conc will double at each time point.
When the dose is higher, VD will
A. Increase
B. Not change
C. Decrease
B. Not change - LINEAR kinetics = Vd is independent of concentration
Q. T/F: In linear kinetics, AUC is proportional to dose
True
Q: Linear: As time passes after drug admin, Kel will
A. Increase
B. Not change
C. Stay the same
B. Not change - linear = independent
Q. T/F - IV bolus: Kel from the data may be of a negative value
False - Kel cannot be negative
Q. Linear IV bolus - Which of the following dose NOT increase proportionally with the dose
A. Drug concentration at time = 0
B. Drug concentration at time =4
C. AUC
D. Kel
C - AUC: measure of total exposure to drug over time
