Some drugs do not distribute instantly throughout the body. Instead, they move into different tissues at different speeds. For such drugs, the one-compartment model is not enough. This is where multi-compartment pharmacokinetic models are used. They provide a more realistic explanation of how drugs spread through fast and slow tissues, how blood levels change, and how elimination occurs.
What Are Multi-Compartment Models?
A multi-compartment model divides the body into two or more interconnected compartments based on how quickly the drug distributes. These compartments are not actual anatomical structures but represent groups of tissues with similar drug distribution characteristics.
Why Multi-Compartment Models Are Needed
- Some drugs do not mix instantly in the body.
- There is an early rapid drop in plasma levels due to distribution.
- There is a later slower decline due to elimination.
- Many lipophilic and long-acting drugs follow multi-compartment behavior.
Types of Multi-Compartment Models
1. Two-Compartment Model (Most Common)
This model divides the body into:
- Central compartment: blood, heart, liver, kidneys—high blood flow
- Peripheral compartment: muscle, fat, skin—lower blood flow
After IV administration:
- Drug rapidly enters the central compartment
- Then distributes slowly to peripheral tissues
- Finally, elimination occurs primarily from the central compartment
Concentration–Time Curve in Two-Compartment Model
After IV bolus injection, plasma concentration shows two phases:
1. Alpha Phase (Distribution Phase)
- Rapid drop in plasma level
- Drug moves from blood to peripheral tissues
- Steep decline on graph
2. Beta Phase (Elimination Phase)
- Slow decline in concentration
- Represents metabolism and excretion
- Straight line when plotted on log scale
Mathematical Representation
The plasma concentration can be described as:
C(t) = A·e−αt + B·e−βt
Where:
- A and B = intercepts of distribution and elimination
- α = distribution rate constant
- β = elimination rate constant
Volume of Distribution in Multi-Compartment Models
1. Initial Volume of Distribution (Vc)
Represents central compartment volume.
2. Volume of Distribution at Steady State (Vss)
Includes both central and peripheral compartments.
3. Apparent Volume of Distribution During Terminal Phase (Vβ)
Used when calculating half-life in multi-phase decline.
Characteristics of Multi-Compartment Behavior
- Initial rapid fall = distribution
- Slower fall = elimination
- Different tissues receive the drug at different rates
- Clear separation between early and late phases
Examples of Drugs Following Multi-Compartment Models
- Digoxin
- Thiopental
- Antiarrhythmic drugs (e.g., lidocaine)
- Benzodiazepines
Clinical Significance
1. Loading Dose Considerations
Drugs with slow distribution may cause early toxic levels if the loading dose is too high.
2. Therapeutic Drug Monitoring
Some drugs (e.g., digoxin) need blood levels checked after distribution phase is complete.
3. Predicting Drug Accumulation
Multi-compartment drugs may remain in tissues for long periods, affecting dosing frequency.
4. Understanding Redistribution
Important in anesthesia—for example, thiopental causes quick loss of consciousness but wears off rapidly due to redistribution.
Advantages of Multi-Compartment Models
- More accurate for drugs with complex distribution
- Useful for drugs with long half-lives
- Helps understand early vs late concentration changes
Limitations
- Mathematically more complex than one-compartment models
- Requires more blood samples and data
- Not needed for drugs with simple distribution
Detailed Notes:
For PDF style full-color notes, open the complete study material below: