One-compartment model adequately describes pharmacokinetics of many drugs.

**MULTICOMPARTMENT MODELS**

**(Delayed Distribution Models)**

One-compartment model adequately describes
pharmacokinetics of many drugs. Instantaneous distribution equilibrium is
assumed in such cases and decline in the amount of drug in the body with time
is expressed by an equation with a monoexponential term (i.e. elimination).
However, instantaneous distribution is not truly possible for an even larger
number of drugs and drug disposition is not monoexponential but bi- or
multi-exponential. This is because the body is composed of a heterogeneous
group of tissues each with different degree of blood flow and affinity for drug
and therefore different rates of equilibration. *Ideally, a true pharmacokinetic model should be the one with a rate
constant for each tissue undergoing equilibrium*, which is difficult mathematically.
Multicompartment models are* *thus
based on following *assumptions* –

1. Blood/plasma and the highly
perfused tissues such as tissues such as brain, heart, lung, liver and kidneys
constitute the **central compartment**.

2. Other tissues with similar
distribution characteristics are *pooled*
together to constitute **peripheral
compartments **tissues on the basis of similarity in their distribution** **characteristics.

3. Intravenously administered
medications are introduced directly into the central compartment.

4. Irreversible drug elimination,
either by hepatic biotransformation or renal excretion, takes place only from
the central compartment.

5. Reversible distribution occurs
between central and peripheral compartments, with a finite time required for
distribution equilibrium to be attained.

6. After drug equilibration between
drug and the peripheral compartments, elimination of drug follows first-order
kinetics.

7. All rate processes involving
passage of drug in and out of individual compartment are first-order processes
and plasma level-time curve is best described by sum of series of exponential
terms each corresponding to first-order rate processes associated with a given
compartment.

8. The peripheral compartment is
usually inaccessible to direct measurement and is not a site of drug
elimination or clearance

Multicompartment characteristics of a drug are best
understood by giving it as i.v. bolus and observing the manner in which the
plasma concentration declines with time. The number of exponentials required to
describe such a plasma level-time profile determines the number of kinetically
homogeneous compartments into which a drug will distribute.

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