Exam 3: IV Dosing Flashcards
Importance of Pharmacokinetics
- Drug concentration does not reach toxic levels
- Drug concentration is in the therapeutic range
- The duration of effect leads to practical dosing
Importance of half life
After 1 half life, 50% of the drug is eliminated
After 2 half lives, 75% of the drug is eliminated
After 3 half lives, 87.5% of the drug is eliminated
And so on-> keeps decreases by 1/2
Fraction remaining formula
(1/2) ^x
IV Bolus uses what order elimination
Whats the eqaution?
1st order
Ct = C0 * e^-kt
Taking the ln of equation makes it linear
What ADME processes help with elimination
Metabolism and Excretion
Elimination processes begin immediately
Drug infusions
In an infusion, the plasma concentration won’t reach therapeutic range immediately
- We are introducing the drug gradually into
the circulation
Loading dose
Bolus dose needed to immediately yield a
plasma concentration of drug in the therapeutic range
Maintenance dose
Infused dose needed to maintain a plasma
concentration of drug in the therapeutic range
When a drug is being administered it is->
simultaneously being eliminated
Starting an infusion
- Rate of administration>Rate of elimination
* Drug accumulates in the plasma
At Steady state
Rate of administration=Rate of elimination
The plasma drug concentration doesn’t change
How many half lives does it take to reach steady state?
5
Multiple doses - IV bolus
Usually, more than a single dose is needed
- In the graph, concentration of drug goes up and down
Peak concentration
The high concentration following a dose is known as the peak concentration
Known as Cmax
Trough concentration
The low concentration following a dose is known as the trough concentration
Known as Cmin
Intermittent Dosing
Repeated administration of bolus dose
- single dose usually given over <5 min
-Peak concentration reached rapidly
- Elimination reduces plasma drug levels
• Trough concentrations may be below the
MEC
Sub-therapeutic
area below the MEC
Goal of dosing
maintain plasma conc. within therapeutic window
Dosing interval τ
time that elapses between doses
C0 is the
- initial plasma conc.
- also peak conc.
- = to Cmax
Ct
concentration after time t
- conc. of drug just before the next dose
- also trough conc.
- = Cmin
t in equation represents
the time that elapses
τ
the time interval between dose n and dose n+1
t1/2= τ and t1/2 > τ
drug accumulates
If our half life is long relative to τ, then
drug can accumulate in the plasma
If 5*t1/2 >τ
Drug doesn’t accumulate in plasma
Calculating Drug Accumulation
The concentration remaining after the 1st dose is additive with the concentration of the second dose
Loading Dose
• Initial higher dose given to rapidly yield a plasma concentration of drug in the
therapeutic range
CP = Desired peak [Drug]
IV Infusion – Rate of administration
When starting an IV dose,
the drug concentration in the plasma is zero
As drug administration starts->
the plasma drug concentration increases
In IV infusion, the rate of administration (Ra)
is greater than the rate of elimination (Re)
- drug accumulates
Ra > Re
Rate of administration is
how much we introduce per unit time
- Ra
Rate of administration formula
dose (mg) / time (hr)
Administration process occurs by
zero-order kinetic
Elimination process occurs by
first-order kinetic
Change in drug concentration
rate of elimination - rate of administration
When the rate of administration exceeds the rate of elimination ->
the rate of change of drug concentration is the difference between these rates
The rate of elimination is dependent on
the clearance and the plasma drug conc.
Rate of elimination equation
Re = Cl * Conc.
Clearance equation
Cl= Ke *Vd
Steady state
the rate of drug going in is equal to the rate of drug going out
rate of administration = rate of elimination
rate of administration formula
dose/t
rate of elimination fromula
[C]ss*Cl
What Happens Before Steady State
The concentration initially rises with time
• As time increases, we start to see the concentration plateau off
• The plateau concentration is that at steady state (Css)
What Happens Before Steady State
The concentration at time t (Ct) is less than that at steady state (Css)
To calculate Ct , we use the following equation
• Ct =Css*(1-e^-kt)
As time increases, (1-e-kt) approaches
1
Conc. at steady state formula
[C]ss =(dose/t)/ Cl
