Description
Intravenous Infusion
Intravenous (IV) Infusion
• Intravenous drug solutions may be infused slowly through a vein into the plasma at a constant or zero-order rate.
• The main advantage are:
• IV infusion allows precise control of plasma drug concentrations.
• Fluctuations between maximum and minimum plasma drug concentrations can be controlled by IV infusion for drugs with narrow therapeutic window (eg, heparin).
• 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.
• One-compartment model – IV infusion
• Steady-state drug concentration and time needed to reach CSS
• Loading dose plus IV infusion
• Two-compartment model – IV infusion
• Loading dose for two-compartment Model
Biopharmaceutics And Pharmacokinetics
- Subject:- Biopharmaceutics And Pharmacokinetics
- Course:- B.pharm (pharmacy),
- Semester:- 6th sem , sem :- 6
Intravenous Infusion
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Intravenous (IV) Infusion
• Intravenous drug solutions may be infused slowly through a vein into
the plasma at a constant or zero-order rate.
• The main advantage are:
�IV infusion allows precise control of plasma drug concentrations.
�Fluctuations between maximum and minimum plasma drug concentrations can be
controlled by IV infusion for drugs with narrow therapeutic window (eg, heparin).
�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.
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The plasma drug concentration-versus-time curve of a drug given by constant
IV infusion is shown in the figure below.
Because 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
• Plasma
reached. At steady state, the rate of
Level
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 plasma drug
concentration dCP/dt = 0.
Time
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One-compartment model – IV infusion
• For one compartment, pharmacokinetics of a drug by constant IV infusion
follows zero-order input directly into the systemic blood circulation, however,
the output rate will be first-order, i.e. first-order elimination rate. The change
in the amount of drug in the body at any time (dDB/dt) during the infusion is
the rate of input minus the rate of output. dD B
 R inf ï€ kD B
dt
• Integration of above equation gives:
CP 
R inf
1 ï€ e 
ï€ kt
VD k
• At infinite time, t = ∞, e-kt approaches zero, R inf R inf
C ss  
VD k Cl
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Steady-state drug concentration and time
needed to reach CSS
CSS = Rinf/VD.k If a drug is given as a continuous intravenous
infusion, serum concentrations increase until a
steady-state concentration (Css) is achieved. When the
infusion is discontinued, serum concentrations
decline in a straight line if the graph is plotted on
semi-logarithmic axes. The elimination rate constant
(k) can be computed using the following formula:
slope =−k/2.303
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In clinical practice, the steady-state is considered to be
reached after five half-lives.
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If a drug is given at a more rapid infusion rate, a higher steady-state
drug concentration is obtained but the time to reach steady-state is
the same.
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Loading dose plus IV infusion
• The time required to obtain steady-state plasma levels by IV infusion will be
long. It is possible to administer an intravenous loading dose to attain the
desired drug concentration immediately and then attempt to maintain this
concentration by a continuous infusion.
• For a one-compartment drug, if the loading dose (DL) and infusion rate(Rinf) are
calculated such that initial dose (C0) and CSS are the same and both DL and
infusion are started concurrently, then steady state and CSS will be achieved
immediately after the loading dose is administered.
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Two-compartment model – IV infusion
• Many drugs given by IV infusion follow two-compartment kinetics. For example,
the respective distributions of theophylline and lidocaine in humans are described
by the two-compartment open model. With two compartment model drugs, IV
infusion requires a distribution and equilibration of the drug before a stable blood
level is reached. During a constant IV infusion, drug in the tissue compartment is in
distribution equilibrium with the plasma; thus, constant CSS levels also result in
constant drug concentrations in the tissue; i.e., no net change in the amount of
drug in the tissue occurs at steady state.
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Loading dose for two-compartment Model
• Drugs with long half-lives require a loading dose to more rapidly attain steady-state
plasma drug levels. It is clinically desirable to achieve rapid therapeutic drug levels by
using a loading dose. However, for drugs that follow the two-compartment
pharmacokinetic model, the drug distributes slowly into extravascular tissues. Thus,
drug equilibrium is not immediate.
Plasma drug level after various loading doses and rates of
infusion for a drug that follows a two-compartment model:
a, no loading dose;
b, loading dose = R/k (rapid infusion);
c, loading dose = R/b (slow infusion); and
d, loading dose = R/b (rapid infusion).
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Thank you
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