In an intravenous infusion, a drug is delivered slowly and continuously into the bloodstream at a controlled rate. Unlike IV bolus dosing, where the entire dose enters the body instantly, IV infusion maintains stable plasma levels over time. The one-compartment open model for IV infusion explains how drug concentration rises, reaches steady state, and declines after stopping the infusion.
What Is Intravenous Infusion?
IV infusion delivers a drug directly into systemic circulation at a fixed rate (R0). Input is zero-order because the drug enters at a constant rate, while elimination follows first-order kinetics (a constant fraction removed per unit time).
Key Concepts in the Model
1. Zero-Order Input
The infusion rate remains constant regardless of drug concentration.
2. First-Order Elimination
The body eliminates the drug at a rate proportional to its concentration.
3. No Absorption Phase
The drug enters directly into circulation, making calculations easier.
Plasma Concentration–Time Profile
During infusion, plasma concentration gradually increases. It does not rise indefinitely; instead, it approaches a plateau called the steady state. When the infusion stops, the concentration declines exponentially just like an IV bolus dose.
Steady State (Css)
Steady state is reached when the rate of drug input equals the rate of elimination. Once reached, the plasma level remains constant as long as the infusion continues.
Equation for Steady-State Concentration
Css = R0 / Cl
Where:
- R0 = infusion rate (mg/hr)
- Cl = clearance (L/hr)
Time to Reach Steady State
Steady state is achieved after approximately 4–5 half-lives, regardless of infusion rate.
Important Points
- Increasing the infusion rate changes Css but does not change how fast steady state is reached.
- Half-life determines how quickly steady state occurs.
Concentration During Infusion
The concentration at any time (t) during infusion is calculated as:
Ct = Css (1 − e−kt)
Interpretation
- The curve rises quickly at first
- Then slowly approaches steady state
Concentration After Stopping the Infusion
When infusion stops, drug concentration decreases exponentially:
Ct = Css · e−kt
Loading Dose with Infusion
Some drugs have long half-lives (e.g., digoxin, theophylline). To achieve therapeutic levels faster, a loading dose may be given.
Loading Dose = Ctarget × Vd
Factors Affecting Intravenous Infusion Pharmacokinetics
- Infusion rate: directly changes steady-state concentration
- Clearance: higher clearance → lower Css
- Half-life: determines time to steady state
- Volume of distribution (Vd): affects loading dose
Clinical Applications
1. Maintaining Constant Drug Levels
Useful for drugs with narrow therapeutic windows (e.g., lidocaine, heparin).
2. Intensive Care and Emergency Treatment
Allows tight control of plasma concentration for critically ill patients.
3. Drugs with Short Half-Lives
Continuous infusion helps maintain therapeutic effect without frequent dosing.
4. Therapeutic Drug Monitoring (TDM)
Infusion models help guide dose adjustments based on measured plasma levels.
Advantages of intravenous Infusion
- Provides stable drug concentrations
- Prevents peaks and troughs seen with bolus dosing
- Allows precise control in emergencies
Limitations
- Requires infusion equipment (pump or drip)
- Risk of infection at injection site
- Not suitable for all drugs or outpatient settings
Detailed Notes:
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