Saturation of the absorption rate
In some cases, for instance in case of transporter-mediated uptake, the absorption from the depot compartment into the central compartment can saturate. To model this phenomenon, one can replace the first-order rate of absorption by a Michaelis-Menten term.
Examples of drugs displaying a saturating absorption include Phenylbutazone, Naproxen, Chlorothiazide, beta-lactam antibiotics and are reviewed in:
Mlxtran model
To describe a saturable absorption, the depot compartment must be explicitly described and the model must be written as an ODE system. Below we present a one-compartment model with linear elimination and saturable absorption.
The depot macro permits to add the doses defined in the data set to the amount in the depot compartment. The Michaelis-Menten term is written using the amount of the depot compartment instead of the concentration as the volume needed to calculate the concentration is unidentifiable.
[LONGITUDINAL]
input={Vm, Km, V, Cl}
PK:
depot(target=Ad)
EQUATION:
t_0 = 0
Ad_0 = 0
Ac_0 = 0
ddt_Ad = -Vm*Ad/(Ad+Km)
ddt_Ac = Vm*Ad/(Ad+Km) - Cl/V*Ac
Cc = Ac/V
OUTPUT:
output = {Cc}