Intravenous Infusion

INTRAVENOUS INFUSION
"Drug administration through the intravenous route at a constant rate over a

determined time interval."
Introduction
Pharmacokinetics is the science of the kinetics of drug
absorption, distribution, and elimination (i.e., metabolism and
excretion). Kinetics is the study of the rate of a process and
the factors affecting on it. The rate of a process is the change
in velocity or speed with (in relation to) time.
Drugs may be administered to patients by oral, topical, parenteral, or other various routes
of administration.
Drugs administered by IV route may either be given at once (as a bolus dose) or by slower
IV infusion over a definite time such as Phenytoin which must be given slowly, no greater
than 50 mg/min (and preferably 25 mg/min or less) in adults. Such drugs are infused
slowly through a vein into the blood at a constant rate (zero order input) which allows
precise control of plasma drug concentrations. Drugs may be administered to patients by
one of various routes including oral, topical, or parenteral routes of administration.
In clinical practice, drugs are given by continuous infusion to maintain a predictable

pharmacodynamic action. In anesthesia, the most common route is by continuous i.v.
infusion, but the extradural, subarachnoid and subcutaneous routes are also regularly
used. The effective use of drug infusions requires an understanding of both the
pharmacokinetic and pharmacodynamic characteristics of the drug used.
Pharmacokinetics describe how the plasma concentration of a drug changes over time,
with the assumption that plasma will equilibrate with an effect compartment to produce
pharmacodynamic activity.
Examples of parenteral routes of administration
Examples of parenteral routes of administration include intravenous, subcutaneous, and

intramuscular. Intravenous (IV) drug solutions may be given either as a bolus dose
(injected all at once) or infused slowly through a vein into the plasma at a constant or
zero-order rate.
Difference Between IV Bolus and IV Infusion
The term “intravenous bolus” is usually used to specify either 1) set volume or 2) a faster
speed, or 3) both. The most common use of the term is for a patient with low blood
pressure, a doctor may order a “bolus” of a 1 or 2 liters (set volume) of IV fluids to be
given rapidly (speed) to increase the patient’s blood pressure.
The term “IV infusion” implies that a medication or fluid will be given in a slower pace, or
for a large or indeterminate period of time. For instance, I may order IV fluids to run at
100mL/hr (slow speed, no specified volume). Even if I order 1 liter of IV fluids at 100mL/hr
it would still take 10 hours, so it’s typically referred to as an infusion.
Advantages:
 The main advantage for giving a drug by IV infusion is that IV infusion allows
precise control of plasma drug concentrations to fit the individual needs of the
patient.
 For drugs with a narrow therapeutic window (eg, heparin), IV infusion maintains an
effective constant plasma drug concentration by eliminating wide fluctuations
between the peak (maximum) and trough (minimum) plasma drug concentration.
 Moreover, the IV infusion of drugs, such as antibiotics, may be given with IV fluids
that include electrolytes and nutrients.
 Furthermore, the duration of drug therapy may be maintained or terminated as
needed using IV infusion.
For an i.v. infusion, plasma concentrations are influenced by distribution, redistribution,

metabolism and excretion. For other routes of administration, absorption must also be
considered. Elimination is a non-specific term describing any process that removes drug
from plasma.
There are several processes contributing to elimination: distribution describes elimination

attributable to a drug temporarily being taken up by tissue other than plasma;
redistribution is the release of such temporary stores back to plasma; and excretion the
processes that permanently removes a drug from the plasma.
Excretion is therefore a combination of metabolism (producing metabolites) and excretion

of unchanged drug (e.g. from the kidneys or lungs). Metabolism to active products may
prolong duration of action, thus altering the relationship between plasma concentration of
a drug and pharmacodynamic activity.
At time zero, no drug was present in the body after which the drug level gradually
increases until it becomes constant (plateau or steady-state). Once the drug has reached
the steady-state, the rate of drug leaving the body is equal to the rate of drug entering the
body.
Rate of drug input = rate of drug output

(infusion rate) (elimination rate)
The factors affecting the steady state plasma drug concentration are:
1. Infusion rate (Ro): The steady state drug concentration is proportional to the
infusion rate. Thus, a higher infusion rate will result in a higher steady state plasma
drug concentration.
2. Clearance: Higher clearance of the drug will result in lower plasma drug
concentration at plateau.
The following figure represents the plasma-level time curve for a drug given by constant
IV infusion.
Figure 1: Plasma-concentration time curve during the infusion of the administered drug at
constant rate
Clinical Pharmacokinetics implications of IV Infusion:
The constant rate infusion regimen is used to ensure a constant exposure to the drug
over a prolonged time. The drug infusion rate must be adapted to the patient's clearance
in order to have the concentration reach a therapeutic target
 The mathematical expression or the pharmacokinetic equation for drug

administered by infusion will depend on whether the drug follows the one- or two-
compartment model.
One-Compartment IV Infusion
Drugs administered by constant IV infusion show a zero-order input process, during which
the drug is introduced into the bloodstream while the elimination process for most drugs
is first-order. The rate of input minus the rate of output represents the change in the
amount of drug in the body at any given time (dDB/dt) .
Figure 2: Plasma-concentration time curve after IV Infusion
If DB is the amount of the drug in the body, R is the rate of drug input (infusion rate) and
k is the elimination rate constant. The expression that best describes the process is:
dDB/dt = R – k DB
DB = CPVD
Integration of the last equation will give:
CP= [R/VDk] (1− e−kt)
Steady-State Drug Concentration (CSS) and Time to Reach

Steady-State
During administration of a drug by IV infusion, the plasma drug concentration starts to

increase and the rate of drug elimination will also increase since the latter is
concentration-dependent. Cp keeps increasing until a steady-state condition is reached
at which the rate of drug input (IV infusion rate) equals the rate of drug output (elimination
rate). At this stage, a steady-state (CSS) is reached and the resulting plasma drug
concentration is directly related to the rate of infusion and inversely related to the body
clearance of the drug.
For drug administered by IV infusion, the therapeutic activity is observed when the
concentration of the drug is close to the desired plasma concentration, which is usually
the required steady-state drug concentration.
Loading Dose plus IV Infusion (Combined Infusion and Bolus

Administration)
If we desire to achieve a quick therapeutic concentration, a loading dose by rapid

intravenous injection (bolus injection) is first administered and then starts the slower
maintenance infusion. At this condition, the total drug concentration in the plasma is the
function of both; the IV bolus and the infusion doses.
Intravenous Infusion of Two-Compartment Model Drugs
Some drugs such as lidocaine and theophylline when administered by IV infusion do not
follow the one- but rather the two-compartment model. As has been discussed in the IV
bolus, during a constant IV infusion, the drug in the tissue compartment is in distribution
equilibrium with that in the plasma and a steady state concentration is reached during
equilibrium.
Apparent Volume of Distribution at Steady State, Two-
Compartment Model
The amount of the drug in the body at steady-state is the product of the plasma
concentration and the steady-state volume of distribution (VD)ss.
Mean effect time:
A different approach to offset of action after an infusion is discontinued is the probabilistic

approach described by Bailey. This uses a logistic regression model to predict the time it
would take drug effects to disappear in 50% of patients. It is perhaps a more useful clinical
predictor, but unfortunately there are relatively few data available for commonly used
drugs. The advantage of such an approach is that it is more pharmacodynamic than
pharmacokinetic.
Drugs typically given by IV
Antibiotics such as vancomycin, meropenem, and gentamicin. Antifungal drugs such as

micafungin and amphotericin. Pain medications such as hydromorphone and
morphine. Drugs for low blood pressure such as dopamine, epinephrine, norepinephrine,
and dobutamine.
References:
 Applied Biopharmaceutics & Pharmacokinetics Seventh Edition EDITORS Leon

Shargel
 https://www.intechopen.com/books/basic-pharmacokinetic-concepts-and-some-
clinical-applications/pharmacokinetics-of-drugs-following-iv-bolus-iv-infusion-and-
oral-administration
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339323/
 https://sepia.unil.ch/pharmacology/index.php?id=68&L=0%2520then%2520para
meters%2520the%2520bioavailability

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What are the main differences between IV bolus and IV infusion?

What are the main differences between IV bolus and IV infusion?

What are some advantages of IV infusion compared to other routes of drug administration?

What are some advantages of IV infusion compared to other routes of drug administration?

INTRAVENOUS INFUSION

"Drug administration through the intravenous route at a constant rate over a

In clinical practice, drugs are given by continuous infusion to maintain a predictable

Examples of parenteral routes of administration

Examples of parenteral routes of administration include intravenous, subcutaneous, and

For an i.v. infusion, plasma concentrations are influenced by distribution, redistribution,

There are several processes contributing to elimination: distribution describes elimination

Excretion is therefore a combination of metabolism (producing metabolites) and excretion

Rate of drug input = rate of drug output

Clinical Pharmacokinetics implications of IV Infusion:

 The mathematical expression or the pharmacokinetic equation for drug

Figure 2: Plasma-concentration time curve after IV Infusion

Integration of the last equation will give:

CP= [R/VDk] (1− e−kt)

Steady-State Drug Concentration (CSS) and Time to Reach

During administration of a drug by IV infusion, the plasma drug concentration starts to

Loading Dose plus IV Infusion (Combined Infusion and Bolus

If we desire to achieve a quick therapeutic concentration, a loading dose by rapid

Intravenous Infusion of Two-Compartment Model Drugs

Mean effect time:

A different approach to offset of action after an infusion is discontinued is the probabilistic

Drugs typically given by IV

Antibiotics such as vancomycin, meropenem, and gentamicin. Antifungal drugs such as

 Applied Biopharmaceutics & Pharmacokinetics Seventh Edition EDITORS Leon

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