V max represents the maximum elimination rate of the system. One common way to represent this phenomenon is to use a Michaelis-Menton kinetic model, like the one shown below:Ĭlearance is a function of the concentration of drug which changes over time. Once the amount of drug exceeds the capacity of the enzyme to metabolize it, you begin to see non-linearity. This can happen if the mechanism of clearance is dependent upon an enzyme system with fixed capacity. Most often, the non-linearity is due to a saturation of a clearance mechanism. Nonlinear PK occurs when clearance is not constant (i.e. If clearance is not changing, then exposure increases linearly with Dose. Both describe the same set of conditions. This is why the term “constant clearance” is often substituted for the term “linear PK”. If clearance is constant, then increases in Dose are directly proportional to increases in AUC. The following equation shows the relationship between Dose, AUC (exposure) and CL (clearance): The reason for the non-linearity is related to the clearance of the drug from the body. When the dose of EPO is doubled from 1 μg/kg to 2 μg/kg, the exposure increases more than 2-fold. For a drug with linear PK, we would expect that a 2-fold increase in dose would result in a 2-fold increase in drug exposure. Nonlinear PK means that increases in drug exposure are not linearly related to increases in administered doses. EPO is a common PED for cyclists, runners, and other endurance sports.īut the use of EPO has nothing to do with the nonlinear PK that it exhibits when administered to humans. Athletes use EPO to gain a competitive advantage by increasing the oxygen transport capacity in their body and thus increasing endurance. Patient who undergo chemotherapy often receive EPO to help boost red blood cell production to replace the cells lost during the chemotherapy regimen. EPO regulates red blood cell production, and it is used therapeutically to stimulate bone marrow to produce more red blood cells. You may have heard about EPO in the context of sports because it is a performance enhancing drug (PED). An example of a drug that has nonlinear pharmacokinetics (PK) is erythropoietin or EPO. You may come across a phrase like the following and wonder what it means: “… this drug exhibits nonlinear pharmacokinetics …”.
0 kommentar(er)
