Chapter 17 - Page 4 Graph 3

Linear Plot of Cp versus Time after a Single Oral Dose Administration One Compartment Model - Liver Metabolism Models



Hepatic clearance can be calculated from three parameters according the well stirred model and the parallel tube model. These parameters are intrinsic, unbound clearance (CLint), fraction unbound (fu) and hepatic blood flow (QH). The equations for these two models are different but they contain the same three parameters.

Equation 17.2.1 Hepatic Clearance according to the Well Stirred Model

Equation 17.2.2 Hepatic Clearance according to the Parallel Tube Model

Table of Parameter Values that might be useful with this simulation

Parameter Example Value Range of Values Comment
F*Dose 100 mg 100 mg ± Linear system in this example
Absorption Rate Constant 1.5 hr-1 0.1 - 10.0 hr-1  
Volume of Distribution
V
20 L 7 - 200+ L  
Excretion Rate Constant
ke
0.05 hr-1 0 - 5+ hr-1 Non hepatic excretion/elimination
Unbound Intrinsic Clearance
CLint, ub
10 L/hr 0 - 1500+ L/hr Shargel and Yu, 3rd, 1993
Hepatic Blood Flow
QH
80 L/hr 60-120 L/hr 70 Kg adult, Shargel and Yu, 3rd, 1993
Fraction unbound, in blood
fu, b
0.5 0 - 1  

Equations used in this simple pharmacokinetic model.

Equation 17.2.3 Elimination Rate Constant as a function of CLH, V and ke

Cp versus time after oral dose

Equation 17.2.4 Concencentration versus Time after a single Oral Dose

Equation 17.2.5 Extraction Ratio calculated from CLH and QH

Explore flow limited drug behavior by setting CLint somewhat larger (> 200 L/hr) than the hepatic blood flow rate. Change QH, fu and CLint to see which parameters have the greatest influence of half-life and AUC. Capacity limited drug behavior can be explored by setting CLint to a lower value (< 40 L/hr). Explore the effect of V on drug half-life.

Explore the equation by changing the parameter(s). Add additional lines with different parameter values using the Add Line button.


References


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