Introduction
The one compartment open model is one of the simplest and most commonly used pharmacokinetic models. It is especially useful for understanding how a drug behaves after it is given as a single (intravenous injection) intravenous (IV) bolus dose. In this model, the body is treated as a single, uniform compartment where the drug distributes instantly and is removed from the body through elimination processes such as metabolism and excretion.
What Is the One Compartment Open Model?
It assumes that once the drug enters the bloodstream, it mixes instantly and uniformly throughout the body. There is no delay in distribution, and elimination begins immediately. The term “open” means that the drug leaves the body through elimination pathways.
Why (intravenous injection) IV Bolus Is Easy to Model
In IV bolus administration, the entire dose is injected directly into systemic circulation at one time. There is no absorption phase. Therefore, the pharmacokinetic process begins directly with elimination and distribution.
Assumptions of the Model
- The body behaves like a single, well-mixed compartment.
- Distribution throughout the body is instantaneous.
- Elimination follows first-order kinetics (constant fraction removed per unit time).
- Drug concentration is proportional to plasma concentration.
Plasma Concentration–Time Profile
After an IV bolus dose, the drug concentration declines exponentially. When plotted on a semi-log graph, this decline appears as a straight line.
Equation
C = C0 · e-kt
Where:
- C = concentration at time t
- C0 = initial concentration right after injection
- k = elimination rate constant
- t = time
Initial Concentration (C0)
Immediately after the bolus dose:
C0 = Dose / Vd
Volume of Distribution (Vd)
Vd represents how extensively the drug spreads in the body. A large Vd means the drug is stored in tissues, while a small Vd means the drug stays mostly in blood.
Half-Life (t1/2)
Half-life is the time required for the concentration of the drug in plasma to fall to half its initial value. It is calculated using:
t1/2 = 0.693 / k
Clearance (Cl)
Clearance measures how efficiently the body eliminates the drug. It is given by:
Cl = k · Vd
Graphical Interpretation
When plasma concentration is plotted on a logarithmic scale versus time:
- The curve becomes a straight line.
- The slope of this line equals –k/2.303.
- Extrapolating the line back to time zero gives C0.
Clinical Applications
1. Calculating Loading Dose
For drugs that need a rapid onset, a loading dose is calculated using:
LD = Ctarget · Vd
2. Predicting Drug Levels Over Time
Using the exponential equation, clinicians can estimate how long a drug stays in the body.
3. Adjusting Drug Doses
The model helps adjust doses safely for patients with kidney or liver disease, where elimination is slower.
4. Understanding Toxicity and Therapeutic Window
By predicting plasma concentrations at different times, pharmacists can avoid toxic peaks and maintain effective levels.
Advantages of the One Compartment Model
- Simple and easy to apply.
- Useful for many drugs that rapidly distribute.
- Requires minimal sampling to estimate parameters.
Limitations
- Does not work well for drugs with slow distribution phases (e.g., digoxin).
- Oversimplifies complex physiological processes.
- Assumes instant mixing, which is not always realistic.
Examples of Drugs Approximated by This Model
- Aminoglycoside antibiotics
- Theophylline
- Caffeine
Detailed Notes:
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