For drugs which exhibit non-linear metabolism within their therapeutic range can be difficult to dose. Small changes in dose can result in larger changes in concentration. Using average values for parameters can be a good start but better results can be achieved with therapeutic drug monitoring. Analysis of TDM data can by use of equations or graphical methods. Both types of approaches are described in this tutorial.

Given the requirement that concentrations stay between Cpmax and Cpmin we can calculate a suitable loading dose, maintenance dose and dosing interval.

Three parameters; kel, ke and fe, can estimated from drug in urine data using a semi-log plot of rate of excretion versus time data

Data collected after an IV infusion can be analyzed by plotting the data on semi-log graph paper. The slope will yield a value for kel. The value of V can be determined from Cp(D), the concentration at the end of the infusion.

Three parameters; kel, ke and fe, can estimated from drug in urine data using a semi-log plot of rate of excretion versus time data

After completing the material in this chapter each student should:-

* be able to draw the scheme and write the differential equations for a one compartment pharmacokinetic model with elimination of drug and metabolite into urine (parallel pathways of elimination)

* to use the appropriate integrated equations for this pharmacokinetic model to calculate amount of drug excreted into urine

* be able to plot cumulative amount excreted versus time, A.R.E. versus time and rate of excretion versus time (midpoint) and use these graphs to calculate pharmacokinetci parameters

* be able to define, use, and calculate the parameters:

* * ke (excretion rate constant)

* * km (metabolism rate constant)

* * U∞ and M∞

* * fe and fm

* * renal and non renal clearance

* be able to use fe, the fraction excreted, to calculate overall elimination rate constants in patients with impaired renal function

After completing the material in this chapter each student should:-

* understand the separate assumptions associated with the one compartment model, rapid IV bolus dosing and linear elimination

* understand the properties of first order kinetics, linear models

* be able to write the differential equations for a simple pharmacokinetic model

* be able to define, use, and calculate the parameters:

* * kel (elimination rate constant)

* * V (apparent volume of distribution)

* * t1/2 (half-life)

* * AUC (area under the concentration versus time curve)

* * Cl (clearance)

as they apply to a one compartment linear model

* be able to use the integrated equations for a one compartment linear model to perform various dose and dosing regminen calculations

After completing the material in this chapter each student should:-

* have an basic understanding of the scope and impact of biopharmaceutics and pharmacokinetics

* have a general knowledge of the factors affecting the rate and extent of drug absorption, distribution, metabolism and excretion