# 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 DistributionV 20 L 7 - 200+ L Excretion Rate Constantke 0.05 hr-1 0 - 5+ hr-1 Non hepatic excretion/elimination Unbound Intrinsic ClearanceCLint, ub 10 L/hr 0 - 1500+ L/hr Shargel and Yu, 3rd, 1993 Hepatic Blood FlowQH 80 L/hr 60-120 L/hr 70 Kg adult, Shargel and Yu, 3rd, 1993 Fraction unbound, in bloodfu, 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

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

• Burton, M.E., Shaw, L.M., Schentag, J.J., and Evans, W.E. (editors) 2006. Applied Pharmacokinetics & Pharmacodynamics, Principles of Therapeutic Drug Monitoring, Lippincott Williams & Wilkins, p133
• Kwon, Y. 2001 Handbook of Essential Pharmacokinetics, Pharmacodynamics, and Drug Metabolism for Industrial Scientists, Kluwer Academic/Plenum Publishers, pp 90-95
• Shargel, L., Wu-Pong, S. and Yu, A.B.C. 2005 Applied Biopharmaceutics and Pharmacokinetics, 5th ed., McGraw-Hill, pp 342-343