One-Compartment Open

Model:
Intravenous Infusion
 IV infusion …………………..Uses
• Commonly used in a hospital setting a patient will receive a drug by intravenous
infusion.
• The inconvenience of administering the drug over a long time is not a real problem with
bedridden patients. Some may already be receiving intravenous fluids.

Drug may be added to the fluid and thereby be given by

• If a drug is: slow infusion
• As a solution 1. When High fluid volume is needed:
• chemically stable Hypoglycemia, dehydration, hemorrhage
2. When therapeutic drug level must be reached quickly:
• compatible with the intravenous fluid Critical illness

• Some drugs cannot be given by rapid intravenous injection. Therefore they may be
given by slower IV infusion over 15 or 30 minutes.
• Iv infusion depends on gradual building up drug in the body to reach steady state
concentration
• Using Iv infusion helps to maintain the therapeutic concentration of drug for long period
of time
• In Iv Bolus……elimination starts immediately
• Iv infusion is a smart choice for narrow therapeutic window drugs

We can reverse the side effects if occur immediately

We have:
1. rapid infusion
2. Slow infusion: over 15 or 30 minutes
IV infusion …………….Reasons

• To avoid fluctuations of plasma concentration:

1. To ensure a constant supply of drug such that the drug accumulates in the body
and ultimately reaches steady state concentration within the therapeutic range.
2. To achieve a consistent pharmacologic response/outcome
3. To avoid certain side effects
4. To determine an accurate assessment of the total body clearance.

• The IV infusion of drugs, such as antibiotics, may be given with IV fluids that
include electrolytes and nutrients.

• the duration of drug therapy may be maintained or terminated as needed using IV

infusion. e.g.: General anesthesia
 the infused drug follows zero-order input and first order output.

Rate of
At SS. : Infus. rate= elimin. rate
K0> rate
of K
.
.
.
Zero
order
input:
constant K
amount First order
per time output
(rate) elimination
 Zero order input

Infusion +elimination

Iv bolus
IV infusion

Loading dose+ Infusion +elimination

For long t1/2 drugs

Post-infusion Elimination phase

1st order
Infusion +elimination
 During IV infusion …………….. One compartment open-model
• The dose is administrated by a constant zero-order rate of input (mass/time)
(rate of infusion)

• Drug is eliminated by a first-order process.

B= before steady state

A= at steady state
• No drug was present in the body at zero time

• drug level rises from zero drug concentration and gradually becomes constant
when a plateau or steady-state drug concentration is reached.

• At steady state:

• the rate of drug leaving the body is equal to the rate of drug (infusion rate) entering the
body. Therefore, at steady state:

the rate of change in the plasma drug concentration= 0

Rate of drug input (infusion rate) = rate of drug output (elimination rate)
dCp/dt = 0
 During infusion
(without cessation)
 Calculation of Observed conc. (Cp) at any time during infusion

The change in the amount of drug in the body at any time point (dDB/dt) during the infusion is the rate of
input minus the rate of output

If K0 is high …….. Conc. ….K is high ……. T1/2 is short

Equation 6.2 gives the plasma drug

concentration at any time during the IV
infusion, where t is the time for infusion Css
• In clinical practice, a plasma drug concentration prior to, but asymptotically approaching, the theoretical
steady state is considered the steady-state plasma drug concentration (Css).

• During the IV infusion:

the plasma drug concentration Cp increases and the rate of drug elimination K increases

because rate of elimination is concentration dependent (ie, rate of drug elimination = kCp).
 At Steady state (SS)

We use during infusion equations to derive

steady state equations
Cp keeps increasing until steady state is reached at which time the :
rate of drug input (IV infusion rate) equals rate of drug output (elimination rate).

Rate of K0 = rate of K

The resulting plasma drug concentration at steady state (Css) is related to the rate of infusion
and inversely related to the body clearance of the drug as shown in the equation
 This equation may also be obtained with the following
approach. At steady state, the rate of infusion equals the
rate of elimination. Therefore, the rate of change in the
plasma drug concentration is equal to zero

At S.S= zero 2
1

Inversely
 Calculation of Observed conc. (Cp) at any time using Css

• At infinite time t = ∞…….. e-kt approaches zero at the steady-state drug

concentration (Css) and the equation becomes
At S.S
observed 2 1

Css
• An increase in the infusion rate will not shorten the time to reach the steady-state drug
concentration.

• If the drug is given at a more rapid infusion rate, a higher steady-state drug level will be obtained,
but the time to reach steady state is the same

Higher R….Higher Css ….

but the same tss
Infusion method for calculating :

1. Elimination rate constant …K

2. Elimination half life…. T1/2
 Elimination rate constant calculation…K

eliminating rate constant (K) can be determined by:

• 1. using the followings:

2. estimating slope of:

• the curve resulting from plotting log (Css - Cp) versus time on rectilinear coordinates
• or
• the curve resulting from plotting (Css - Cp) versus time on a semi logarithmic graph paper.
Rate of elimination using Iv
infusion
 Knowing half life is important …..why????

• The Cp-versus-time relationship that occurs during an IV infusion may be used to

calculate k, or indirectly the elimination half-life of the drug in a patient.

• Some information about the elimination half-life of the drug in the population

must be known

• one or two plasma samples must be taken at a known time after infusion.

• Knowing the half-life in the general population helps determine if the sample is

taken at steady state in the patient.

Time to reach steady state calculation using the half-life

Most of drugs need 4-5 t1/2 to

reach SS

Time to reach SS (tss)

=4.32* t1/2
 Practice problem
A physician wants to administer an anaesthetic agent at a rate of 2 mg/h by IV infusion. The elimination
rate constant is 0.1 h-1 and the volume of distribution (one compartment) is 10 L. How much is the drug
plasma concentration at the steady state (Css) ?

K0= 2 mg/h

K= 0.1 h-1

Vd= 10 L

Css= 2mg/L
Loading dose+ Infusion +elimination
 Loading dose plus iv infusion-one-compartment model

The loading dose DL

Amount of drug given at zero time of infusion

initial bolus dose

Time to reach SS (tss) =4.32* t1/2 ….. Longer t1/2 > > > longer tss

is used to obtain desired concentrations as rapidly as possible (Css is the desired

therapeutic effective concentration)

Longer t1/2 drugs need long time to reach S.S

Assume that an IV bolus dose DL of the drug is given and that an IV infusion is started at the same
time.
 In Iv infusion

In Iv bolus = Css =
Css
C 0
 The total concentration Cp at t hours after the start of infusion would be equal to
C1 + C2 due to the sum contributions of bolus and infusion

The concentration of drug in the body for a one-compartment model after an

IV bolus dose (DL) …C1

The concentration of drug in the body for a one-compartment model after an concentration by
In infusion…… C2
Both… C1+C2= simultaneous infusion after a loading dose.
• Another method for the calculation of loading dose DL is based on knowledge of the desired steady-
state drug concentration Css and the apparent volume of distribution Vd for the drug.

• For many drugs, the desired Css is reported in the literature as the effective therapeutic drug
concentration.

• The Vd and the elimination half-life are also available for these drugs.

𝑪𝟎 = 𝑪𝒔𝒔

𝑫𝑳
C0=
𝑽𝒅

𝑫𝑳
Css= 𝑽𝒅
For many drugs, the desired Css is reported in the literature as the effective therapeutic
drug concentration
𝑲𝟎
𝑪𝒔𝒔 =
𝑽𝒅 ∗ 𝑲

𝑫𝑳
𝑪𝟎 = 𝑪𝒔𝒔 =
𝑽𝒅

𝑲𝟎 𝑫𝑳
=
𝑽𝒅 ∗ 𝑲 𝑽𝒅

𝑲𝟎
𝑫𝑳 =
𝑲
DL= 353 mg (Iv bolus Dose)

K0= 60 mg/h

K= 0.17 h-1

Vd= 25 L

Calculate:

1. T1/2

2. Css

3. Cp at t= 6hr
1. T1/2: 𝟎.𝟔𝟗𝟑
T1/2=
= 4.08 hr 𝑲

2. Css:
DL= Css∗ Vd
= 14.12 mg/L
3. Cp at t= 6hr

You have to find if this sample was taken before SS or after SS ???

before SS drug from Iv bolus is remaining and CSS= C1 (bolus) + C2 (infusion)

Time to reach S.S = 5*t1/2 …. 5*4.08= 20.4 hr ……… So this sample is before SS

Cp= 14.12 mg/L

 Post-infusion
(with cessation)
We use:
• During infusion equation
• IV Bolus equation

to derive post infusion equations

HOW???
 Post infusion

(Rate)K0 = (rate)K
0 K0= KDB

K=0.693/t1/2

(Rate)K0 >> (rate)K

 1. Calculate if cessation is done before or after SS….how??
Tss=4.32 *t1/2
Then:

1. If the cessation of infusion was after achieving steady state

t= time of Cp after cessation time

As after cessation is similar to

IV Bolus elimination…..

C0
2. If the cessation of infusion was before attaining the steady state
level

t= time of Cp after
T= infusion time cessation time
 Or:
1. Calculate Cp at cessation time using during infusion equation …. Cpt=at cessation time

t= cessation time
Cpt= at cessation time

2. Consider Cpt= at cessation time as Cp0 for Cp after cessation

For Cp after cessation (Cp)….. Cp0 = Cpt= at cessation time

3. Then use Iv Bolus equation to calculate Cp after cessation

Cpt= at cessation time
t= time of Cp after cessation time
Cp after cessation
 Cpt= cessation time

Cp after cessation

t= time of Cp after cessation time

t= cessation time
 Post infusion on Semi log
Remember:
If cessation is after steady state:

C0 = Css
t= time of Cp after
cessation time
 Practice problems
• A physician wants to administer an anesthetic agent at a rate of 2 mg/h by IV infusion. The elimination rate
constant is 0.1 h-1 and the volume of distribution (one compartment) is 10 L. How much is the drug plasma
concentration at the steady state? What loading dose should be recommended to reach steady state immediately?

• Solution