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
With linear disposition pharmacokinetic models (distribution, metabolism and excretion first order) it is possible to add concentration from various doses together to get the total drug concentration. Various types of doses can be included at various times.
With linear disposition pharmacokinetic models (distribution, metabolism and excretion first order) it is possible to add concentration from various doses together to get the total drug concentration. Various types of doses can be included at various times.
Given the requirement that Cpmax and Cpmin are close to but below specified values we can calculate a suitable loading dose, maintenance dose and dosing interval.
Given the requirement that Cpmax and Cpmin are close to but below specified values we can calculate a suitable loading dose, maintenance dose and dosing interval.
The parameter values kel and V can be determined from the 'best-fit' line drawn through the data on semi-log graph paper.
Given the requirement that concentrations stay between Cpmax and Cpmin we can calculate a suitable loading dose, maintenance dose and dosing interval.
The absorption parameters, ka and V/F, can be determined from oral data. For good estimates of these parameters the ratio between ka and kel must be greater than 5. Also the absorption and elimination should be first order
Calculating the Area under the Concentration versus Time curve (AUC) using the trapezoidal rule
Calculating the Area under the Concentration versus Time curve (AUC) using the trapezoidal rule
The parameter values kel and V can be determined from the 'best-fit' line drawn through the data on semi-log graph paper.
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.
The absorption parameters, ka and V/F, can be determined from oral data. For good estimates of these parameters the ratio between ka and kel must be greater than 5. Also the absorption and elimination should be first order