Intravenous

Infusion- part 2
 Loading Dose Plus IV Infusion: One Compartment Model

The loading dose DL, or initial bolus dose of a drug, is used to

obtain desired concentrations as rapidly as possible

The concentration of drug in the body for a one-

compartment model after an IV bolus dose is described by

and concentration by infusion at the rate R is

Assume that an IV bolus dose DL of the drug is given and that

an IV infusion is started at the same time. 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, or
Therefore, if an IV loading dose of (DL= R/k )is given, at the
start of an IV infusion, steady-state plasma drug
concentrations are obtained immediately and maintained
 In order to maintain instant steady-state level ([dCp/dt] = 0),
the loading dose should be equal to R/k.

Curve b, shows the blood level after a

single DL=R/k plus infusion from which
the concentration desired at steady state
is obtained immediately.
If the DL is not equal to R/k, then steady
state will not occur immediately.
Curve a. if the given DL < R/k, the
plasma drug concentration takes longer
to decline to the concentration desired at
steady state,
Curve c, if the DL > R/k, the plasma drug
concentrations will increase slowly to
desired drug levels, but more quickly
than without any loading dose.
loading dose DL can also be calculated, if the desired
steady state drug concentration Css and the apparent
volume of distribution VD for the drug are known,
using the following equestion:

DL = Css VD

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
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?
What is the concentration of a drug at 6 hours after
infusion administration at 2 mg/h, with an initial
loading dose of 10 mg (the drug has a t1/2 of 3 hours
and a volume of distribution of 10 L)?
Calculate the drug concentration in the blood
after infusion has been stopped
This concentration can be calculated in two parts
a) calculate the Cp during infusion 2) calculate
the concentration after the stop of the infusion,
using the IV bolus dose equation (C = C0. e-kt) for
calculations for any further point in time. For
convenience, the two equations can be combined
as follows:

where b = length of time of infusion period,

t = total time (infusion and post-infusion),
t - b = length of time after infusion has stopped. Here, we
assume no bolus loading dose was given.
Example: A patient was infused for 6 hours with a
drug (k = 0.01 h-1; VD = 10 L) at a rate of 2 mg/h.
What is the concentration of the drug in the body 2
hours after cessation of the infusion?
An adult male asthmatic patient (78 kg, 48 years old) with a
history of heavy smoking was given an IV infusion of
aminophylline at a rate of 0.75 mg/kg/h. A loading dose of 6
mg/kg was given by IV bolus injection just prior to the start of
the infusion. Two hours after the start of the IV infusion, the
plasma theophylline concentration was measured and found to
contain 5.8 mg/mL of theophylline. The apparent VD for
theophylline is 0.45 L/kg. (Aminophylline is the
ethylenediamine salt of theophylline and contains 80% of
theophylline base.)

Because the patient was responding poorly to the aminophylline

therapy, the physician wanted to increase the plasma
theophylline concentration in the patient to 10 mg/mL. What
dosage recommendation would you give the physician? Would
you recommend another loading dose?
 where S is the salt form of the drug and F is the
fraction of drug bioavailable. For
aminophylline S is equal to 0.80 and for an IV
bolus injection F is equal to 1.

The maintenance IV infusion rate may be calculated after estimation of the

patient’s clearance, ClT. Because a loading dose and an IV infusion of 0.75 mg/h
aminophylline (equivalent to 0.75 × 0.8 = 0.6 mg theophylline) per kg was given
to the patient, the plasma theophylline concentration of 5.8 mg/L is the steady-
state Css
The new IV infusion rate, R′ in terms of
theophylline, is calculated by
R′ = Css.desired ClT
R′ = 10 mg/L × 8.07 L/h = 80.7 mg/h or
1.03 mg/h/kg of theophylline, which is
equivalent to 1.29 mg/h/kg of
aminophylline.
Example An adult male patient (43 years, 80 kg) is to be given
an antibiotic by IV infusion. According to the literature, the
antibiotic has an elimination t1/2 of 2 hours and VD of 1.25 L/kg,
and is effective at a plasma drug concentration of 14 mg/L. The
drug is supplied in 5-mL ampules containing 150 mg/mL.
A. Recommend a starting infusion rate in milligrams per hour
and liters per hour.
R= Css kV = (14 mg/L)(0.693/2 h)(1.5 L/kg)(80 kg)
= 485.1 mg/h
Because the drug is supplied at a concentration of 150
mg/mL,
(150 mg mL)
(485.1 mg ? ) = 3.23 mL
Thus, R = 3.23 mL/h.
B- Blood samples were taken from the patient at 12, 16, and 24
hours after the start of the infusion. Plasma drug concentrations
were as shown below: From these additional data, calculate the
total body clearance ClT for the drug in this patient.

Because the plasma drug concentrations at 12, 16, and 24 hours

were similar, steady state has essentially been reached.)
Assuming a Css of 16.3 mg/mL, ClT is calculated.
C- Estimate the elimination half-life for the antibiotics in this
patient.
Generally, the apparent volume of distribution (VD) is less
variable than t1/2. Assuming that the literature value for VD is
1.25 L/kg, then t1/2 may be estimated from the ClT.
Any question ????