After a brief introduction to pharmacokinetics and pharmacodynamics, the basic concepts of one- and two-compartment models will be laid out and related to distributive properties of drugs. Drug partition between plasma and red blood cells using data from Baselt is discussed.
Plasma concentration versus time plots will be explored and a logarithm/exponential primer will be reviewed. The student will be able to calculate a volume of distribution and recognize the differences between first and zero order kinetics. Given a graphic representation or raw data, we will calculate the elimination rate constant and relate it to the drug’s half-life, as well as understand and use the concept of area under the curve (AUC). We will use the modeling to calculate the fraction of a dose remaining in the body at any time.
We will explore the relationships between pharmacokinetic parameters and review the pharmacokinetics of chronic dosing. The concept of clearance will be applied with an emphasis on hepatic clearance and extraction ratio (ER(h)). Participants will differentiate drugs with high ER(h) versus drugs with low ER(h).
The effect changes in elimination rate constant, in dosing interval, in dose, in clearance or in volume of distribution have on peak and trough concentrations of drugs used chronically will be studied. An accumulation factor will be defined before reaching steady state, and at steady state.
The students will then explore two-compartment modeling and biexponential equations. Calculation and understanding of and (slopes/ distribution and elimination rate constants) will allow the class to appreciate potential problems in the estimation of a drug half-life and define 3 different volumes of distribution (the central compartment volume of distribution, the volume of distribution based on the area under the curve, and the volume of distribution at steady state). Knowing the formulae used in a scientific paper will help interpreting the role clearance has on these values.
On day 3 we will dive into Non-linear pharmacokinetics and model-independent pharmacokinetic parameters. The goal is to explain the various processes that can result in non-linear pharmacokinetics and describe the relationships between drug concentration, AUC and dose. The students will use the Michaelis-Menten model to predict plasma drug concentrations. Vmax, Km will be calculated and allow prediction of the dose required to achieve a specific steady-state concentration. Total body clearance, formation clearance and mean residence time of a drug will be addressed.
We are looking forward to meeting you online for our annual CFSRE/Uptake Applied Pharmacokinetics!