Lecture 9 - Compartment Models

CHE-30010 Lecture 9 - Natalie 11/02/2021 Compartment models Describes the movement of drugs through the body as individual compartments to characterise transfer rate constants and allows better predictions of the pharmacokinetics of the drug. One compartment model Simplest model, we assume that the body is a single compartment/container – the plasma alone. Assume there is one compartment, there are two rate constants – absorption and elimination from the plasma – two kinetic profiles. If absorption is instantaneous, as with IV injections, then the concentration profile can be described by our simple exponential elimination equation, as it enters the blood stream directly. Two compartment model If we have a second compartment (fat), which can exchange drug material from the first compartment (plasma), then we get more complex kinetic profiles. Consider rate of movement in and out of fat storage – not equal and can change based on the scenario (amount of fat can change and how much it can hold). Depends on the persons weight so can vary – important regarding the therapeutic benefit or toxicity of a drug. DDT – can be held in the fat with no harm, but when it leaves it becomes toxic, so k1 and k2 vastly changes the relative toxicity, based on how well it can be held in fat storage. Distribution depends on the properties of the drug. The more polar/charged the molecule is, the less it will disperse into fat (hydrophobic) in general, so k1 is small. Non-polar drugs prefer to be stored in the fat so k2 is small. CHE-30010 Lecture 9 - Natalie 11/02/2021 Concentration high and drops rapidly (elimination) – expected for a first or second order profile. However, linearising the graph shows that the graph is nonlinear and highlights the two compartments where there is a change in linearity. Left – fast as it is metabolised and taken into storage, losing via elimination and via fat, governed by K1. Right – slow as metabolised drug is replaced by drug coming out of storage. Elimination constant has not changed, but k2 is having an effect. Many compartment model More complex models lead to more complex mathematical analysis for an accurate representation of a drugs metabolic profile. Different organs with different storage systems, metabolic capabilities and saturation points. Kidney, liver and intestines have direct excretion avenues. Use spreadsheets of known data – simplifies it. Without treating as compartments, it is virtually impossible so is essential to work out the metabolic profile, accurately.