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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:

Convolution equation

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.

Multicompartment model

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 Bolus input function
IV Infusion - Continuous Continuous IV Infusion input fucntion
IV Infusion1 IV Infusion input function
Oral2 Oral input function

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 One compartment disposition function
Two1 Two compartment disposition function
Three2 Three compartment disposition function
Four3 Four compartment disposition function

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:

Select your route of administration, sample, and number of compartments:

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 Urine
OR Metabolite Amount in the Central Compartment or Urine
Four Compartment

References


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