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# Convolution

The convolution method described by Benet (Benet, L.Z. 1972 "General Treatment of Linear Mammillary Models with Elimination from any Compartment as Used in Pharmacokinetics," J. Pharm. Sci., 61:536-541) allows the development of the Laplace equation for the amount of drug in the central compartment by a simple multiplication of the input function and the disposition function. A ke/s function can be included to derive the amount of drug in urine. The input function describes the route of administration. The disposition function describes the first order distribution and elimination processes, and on this page, with elimination from the central compartment.

Basically the equation is: Equation 7.7.1 Basic Convolution Equation

A general linear pharmacokinetic model with elimination via excretion into urine (ke), metabolism (km) or other processes (kother) is shown below. Figure 7.7.1 General Multi Compartment Pharmacokinetic Model

In Figure 7.7.1 the plasma or central compartment is red, the tissue compartments are brown, and the urine component of the model is represented by an orange border. Drug is represented by the filled green circles and metabolite by the blue circle. The overall elimination rate constant, kel, is the sum of all the renal excretion, metabolism and other elimination processes, thus kel = ke + km + kother.

### In general the choices we have for the input or route of administration function are:

 Route of Administration Input Function IV Bolus IV Infusion - Continuous IV Infusion1 Oral2 1 This function includes additional flexibility. 'a' represents the time when the infusion is started and 'z' represents the time when the infusion is stopped. If a = 0 and z = ∞ this simplifies to k0/s.

2 The oral dose includes a bioavailability term, F. This is the fraction of the oral dose that is absorbed so F x Dose is the amount of drug which is absorbed into the central compartment.

Functions for more complex absorption processes could be developed.

### Disposition functions include:

 Number of Compartments Disposition Function One Two1 Three2 Four3 1 where
α + β = kel + k12 + k21
and
α x β = kel x k21

2 where
α + β + γ = kel + k12 + k21 + k13 + k31
α x β + α x γ + β x γ = kel x k21 + kel x k31 + k13 x k21 + k12 x k31 + k21 x k31
and
α x β x γ = kel x k21 x k31

3 where
α + β + γ + δ = kel + k12 + k21 + k13 + k31 + k14 + k41
α x β + α x γ + α x δ + β x γ + β x δ + γ x δ = kel x (k21 + k31 + k41) + k12 x (k31 + k41) + k13 x (k21 + k41) + k14 x (k21 + k31) + k21 x k31 + k21 x k41 + k31 x k41
α x β x γ + α x β x δ + α x γ x δ + β x γ x δ = kel x k21 x k31 + kel x k31 x k41 + kel x k21 x k41 + k12 x k31 x k41 + k13 x k21 x k41 + k14 x k21 x k31 + k21 x k31 x k41
and
α x β x γ x δ = kel x k21 x k31 x k41
with help from de Biasi (de Biasi, J. 1989)

An additional Sample Site multiplier can be appled for other sample sites, beyond drug in the central compartment.

### Sample Site functions include:

 Sample Site Function Drug in Central Compartment 1 Drug in Peripheral Compartment1 Drug in Urine Metabolite in Central Compartment Metabolite in Urine 1 x refers to the 2nd, 3rd, or 4th, peripheral, compartment as shown in Figure 7.7.1.

## Let's try it out:

 IV Bolus One Compartment IV Infusion - Continuous Two Compartment IV Infusion Three Compartment Oral Drug Amount in the Central Compartment, the Peripheral Compartment (x) or UrineOR Metabolite Amount in the Central Compartment or Urine Four Compartment

References

• Benet, L.Z. 1972 General Treatment of Linear Mammillary Models with Elimination from Any Compartment as Used in Pharmacokinetics, J. Pharm. Sci., 61(4), 536-541
• de Biasi, J. 1989 Four open mammillary and catenary compartment models for pharmacokinetics studies, J. Biomed. Eng., 11, 467-70