# Chapter 16 - Page 2 - Java 6

## Semi-log Plot of Cp versus Time after a Single Oral Dose Administration One Compartment Model Renal Excretion and Liver Metabolism Models

Renal clearance can be determined from filtration, secretion and reabsorption parameters according to equation 16.2.1. Each of these rates can be explored further in terms of fraction unbound (fU), GFR, renal blood flow (QR), intrinsic secretion clearance (CLisec) and fraction reabsorbed (fR).

Equation 16.2.1 Renal clearance expanded (Bauer, p 14)

Hepatic clearance can be calculated from three parameters according the well stirred model using equation 16.2.2.

Equation 16.2.2 Hepatic Clearance according to the Well Stirred Model

Table of Parameter Values that might be useful with this simulation

 Parameter Value Comment Dose 100 mg ± Linear system in this example Absorption rate half-life, t1/2abs Range 0.1 - 24 hr Fraction absorbedF Range 0 - 1.0 Volume of DistributionV Range 7 - 200+ L Hepatic Blood FlowQH 90 L/hrRange 60-120 L/hr 70 Kg adult, Shargel and Yu, 3rd, 1993 Renal Blood FlowQH 72 L/hr 70 Kg adult, Shargel and Yu, 3rd, 1993 Glomerular Filtration Rate, GFR 0 - 7.8+ L/hr Shargel and Yu, 3rd, 1993 Hepatic Intrinsic ClearanceCLint, ub 0 - 1620+ L/hr Shargel and Yu, 3rd, 1993 Renal Secretion ClearanceCLsec, ub 0 - 39.0+ L/hr Shargel and Yu, 3rd, 1993 Fraction Reabsorbed Renal 0 - 1.0

Equations used in this simple pharmacokinetic model.

Equation 16.2.3 Elimination Rate Constant as a function of CLH, CLR and V

Equation 16.2.4 Absorption rate constant

Equation 16.2.5 Concencentration versus Time after a single IV Bolus Dose

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

References

• Bauer, L.A. 2008 Applied Pharmacokinetics, Second Edition, McGraw-Hill, New York, NY
• 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