Infusion Concepts

though it will take infinite amount of time to reach the TRUE Css for time’s sake we usually accept 90%, 95%, or 99% of the Css being reached

how many half-lives would it take to reach

• 90% of Css

• 95% of Css

• 99% of Css

• 3.3

• 4.32

• 6.65

Advantages of IV Infusion:

• provides precise control over drug ________

• minimal _________ in concentration

• suitable for drugs with ________ _________ _________

• suitable in situations where _____ control over drug administration is required (if a drug must be ____ IMMEDIATELY)

• input

• fluctuation

• narrow therapeutic window

• RAPID stopped

Disadvantages of IV Infusion:

• may take significant time to reach ________ concentration (how is this overcome?)

• restricted for _______ setting

• IV line can be a source of ___________

• therapeutic (overcome by co-administration by IV bolus — loading + maintenance dose)

• institutional

• infection

which equation describes the concentration of a drug undergoing zero order kinetics?

C= Co -k₀t

which equation describes the concentration of a drug undergoing first order kinetics?

C= Co * e^-kt OR

lnC = lnCo -kt

which curve represents 1st order equations when graphed on linear paper?

black = first order

red= zero order

which curve represents 1st order equations when graphed on semilog paper?

red = zero order

black = first order

IV Infusion for ONE COMPARTMENT

• _____- order input

• input rate is ____________ to the amount of drug left in the infusion bag

• ______- order RATE CONSTAT (K0 or Ro) — what are the units?

• zero

• independent

• zero (amount/ time = mg/min)

How do you find the original dose of the infusion?

Dose = Duration of Infusion (time right before elimination) X Infusion Rate

what do the following numbers represent in the one compartment infusion model?

1= k0 (infusion coming into blood in at constant rate)

2= Vd (body as one compartment)

3= Cl = (Ko /Css)

for a given value of clearance the Css is DIRECTLY proportional to _________

rate of infusion

Css = Ko/CL

is Css independent or dependent on half life?

the concentration at steady state is INDEPENDENT on half life BUT

the time to get TO steady state is DEPENDENT on half life (3.3 to 6.65 half lives)

for all drugs having the same rate and having the same clearance the ______ will be the same

Css

Css= Ko/Cl

if Ko and Cl the same Css also same

Ass is dependent on

Vd

because concentration = amount/ vd

amount = concentration * volume

multiply Css by volume to get Ass

the time to reach Css in ONLY controlled by

half life

does the rate of infusion impact the time it takes to reach concentration at steady state?

NO dependent soley on half life

ALWAYS at 3.3 = 90% of Css reached

a useful parameter to describe how long the drugs stay in the body

Mean Residence Time (MRT)

what does the MRT depend on given the constant infusion rate?

the amount of time the drug has spent in the body is dependent on the time the average MOLECULE resides in the body

what are three equations that we can use to solve for mean residence time

MRT = Ass / ko Ass = Css Volume so MRT = Css * Vd / Ko

MRT = 1 / k t_1/2 / ln2 = 1.433 t_1/2

MRT = Vd / Cl Css = Ko/ CL so (Ko/Cl) (vd/Ko) = Vd / Cl

Is MRT or half-life larger?

mean residence time is larger because it is the TOTAL amount of time the durg is in the body wheras half life is the time it take for half of the drug to be eliminated

aslo MRT = 1.44 (halflife) so it will ALWYAS Be larger

how can you find the concentration at any point DURING the infusion?

C= Css (1-e^kT )

how can you find the concentration at any point AFTER the infusion?

C= Css (1-e^-kT ) * e^-k(t-T)

how equation can you use to calculate PK parameters DUIRNG INFUSION when given infusion data?

ln (Css - C) = lnCss - kt

how equation can you use to calculate PK parameters AFTER INFUSION when given infusion data?

lnC = lnCss- kt (regular elimination) Css = Co

how can one achieve Css faster or immediately?

IV Infusion + IV bolus co-administration

except the case of B where C0 = Css the time to reach steady state (plateu) is depended SOLEY on

half life

why would you need to change the rate of the infusion?

• possible adverse reactions

• inadequate therapeutic response

when changing the infusion rate, the new steady state concentration is DEPENDENT on the______ _________ given that Clearance remains constant

the TIME to reach the new steady state will depend soley on

Css depend on

what does the following depict ?

change in infusion rate

Css depends on the new infusion rate if clearance remains the same

time to reach Css depends on half life (3.3 = 90%)

what does the following depict ?

change in infusion rate

Css depends on the new infusion rate if clearance remains the same

time to reach Css depends on half life (3.3 = 90%)