Lecture 1 Two compartment models

Summary

This video script introduces the concepts of one- and two-compartment pharmacokinetic models. It explains how drug distribution and elimination impact plasma drug concentration-time profiles. A one-compartment model suggests rapid distribution and mono-exponential drug decline, with elimination as the only contributing factor. In contrast, a two-compartment model describes slower distribution, leading to a more complex decline in concentration. The script illustrates this with examples of gentamicin and vancomycin, demonstrating how the distribution phase influences the pharmacokinetics and concentration profiles of different drugs.

Takeaways

• 😀 One compartment models describe rapid drug distribution in the body, with a mono-exponential decline in plasma drug concentration.
• 😀 The drug's volume of distribution in a one compartment model is constant and reflects the extent of its distribution.
• 😀 In one compartment pharmacokinetics, the drug distribution is almost instantaneous, and the decline is only due to elimination.
• 😀 Two compartment models are used for drugs that take time to distribute across the body, with the initial volume of distribution being smaller.
• 😀 In two compartment models, drug distribution contributes to the initial steep decline in plasma concentration, followed by a slower decline as the drug distributes further.
• 😀 A two compartment model uses two exponential terms to capture the difference in the initial and later portions of the plasma concentration-time profile.
• 😀 Drugs with two compartment pharmacokinetics, like vancomycin, exhibit a slower distribution phase, which is reflected in the plasma concentration curve.
• 😀 Drugs with rapid distribution, like gentamicin, can be modeled using a one compartment model as distribution is complete by the time the first plasma sample is taken.
• 😀 The distribution phase of a drug in two compartment models contributes to the early decline in concentration, making the curve initially steeper.
• 😀 The rate constants (k-12, k-21, and k10) in a two compartment model help describe the movement of the drug between the central and peripheral compartments.

Q & A

What is the primary difference between one-compartment and two-compartment pharmacokinetics?

The primary difference is that in one-compartment pharmacokinetics, the drug distributes instantly throughout the body, and only elimination affects the drug concentration. In contrast, two-compartment pharmacokinetics involves a slower distribution phase, where both distribution and elimination contribute to the declining drug concentration.

Why does the decline in drug concentration follow a mono-exponential pattern in a one-compartment model?

The decline in drug concentration follows a mono-exponential pattern in a one-compartment model because there is no significant distribution phase, and only elimination is responsible for the drug's decline.

How does the volume of distribution behave in a one-compartment model?

In a one-compartment model, the volume of distribution is a constant value that reflects the extent of the drug's distribution throughout the body, which is assumed to be rapid and essentially instantaneous.

What are the key parameters in a two-compartment model?

The key parameters in a two-compartment model are the rate constants k12, k21 (which describe the movement of the drug between the central and peripheral compartments), and k10 (which relates the amount of drug in the central compartment to elimination).

Why is the initial decline in drug concentration steeper in a two-compartment model?

The initial decline is steeper in a two-compartment model because both distribution to the peripheral compartment and elimination are occurring simultaneously, contributing to a more rapid decrease in concentration early on.

What does the time-concentration curve for gentamicin indicate about its pharmacokinetics?

The time-concentration curve for gentamicin indicates that its distribution is rapid, completing within a few minutes after dosing, which allows its pharmacokinetics to be described with a single volume of distribution and mono-exponential decline.

How does vancomycin's pharmacokinetics differ from gentamicin's in terms of distribution?

Vancomycin's pharmacokinetics differ from gentamicin's in that its distribution phase is slower, which leads to a steeper initial decline in plasma concentration and a more complex multi-exponential decline curve.

What is the role of the rate constant k10 in both one- and two-compartment models?

In both one- and two-compartment models, the rate constant k10 represents the rate at which the drug is eliminated from the central compartment, reflecting the drug's excretion per unit time.

Why is a mono-exponential equation sufficient for some drugs like gentamicin, but not for others like vancomycin?

A mono-exponential equation is sufficient for drugs like gentamicin because their distribution phase is so rapid that it is essentially instantaneous. However, for drugs like vancomycin, where the distribution phase is slower, a more complex multi-exponential equation is needed to describe the concentration-time profile accurately.

What does the steeper initial portion of the plasma drug concentration curve indicate in a two-compartment model?

The steeper initial portion of the plasma drug concentration curve in a two-compartment model indicates that distribution to the peripheral compartment is still happening, in addition to elimination, which causes a rapid decline in concentration before it levels off.